Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.
Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.
A degenerative disorder affecting upper MOTOR NEURONS in the brain and lower motor neurons in the brain stem and SPINAL CORD. Disease onset is usually after the age of 50 and the process is usually fatal within 3 to 6 years. Clinical manifestations include progressive weakness, atrophy, FASCICULATION, hyperreflexia, DYSARTHRIA, dysphagia, and eventual paralysis of respiratory function. Pathologic features include the replacement of motor neurons with fibrous ASTROCYTES and atrophy of anterior SPINAL NERVE ROOTS and corticospinal tracts. (From Adams et al., Principles of Neurology, 6th ed, pp1089-94)
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)
Microtubule-associated proteins that are mainly expressed in neurons. Tau proteins constitute several isoforms and play an important role in the assembly of tubulin monomers into microtubules and in maintaining the cytoskeleton and axonal transport. Aggregation of specific sets of tau proteins in filamentous inclusions is the common feature of intraneuronal and glial fibrillar lesions (NEUROFIBRILLARY TANGLES; NEUROPIL THREADS) in numerous neurodegenerative disorders (ALZHEIMER DISEASE; TAUOPATHIES).
A familial disorder inherited as an autosomal dominant trait and characterized by the onset of progressive CHOREA and DEMENTIA in the fourth or fifth decade of life. Common initial manifestations include paranoia; poor impulse control; DEPRESSION; HALLUCINATIONS; and DELUSIONS. Eventually intellectual impairment; loss of fine motor control; ATHETOSIS; and diffuse chorea involving axial and limb musculature develops, leading to a vegetative state within 10-15 years of disease onset. The juvenile variant has a more fulminant course including SEIZURES; ATAXIA; dementia; and chorea. (From Adams et al., Principles of Neurology, 6th ed, pp1060-4)
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)
A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.
Neurodegenerative disorders involving deposition of abnormal tau protein isoforms (TAU PROTEINS) in neurons and glial cells in the brain. Pathological aggregations of tau proteins are associated with mutation of the tau gene on chromosome 17 in patients with ALZHEIMER DISEASE; DEMENTIA; PARKINSONIAN DISORDERS; progressive supranuclear palsy (SUPRANUCLEAR PALSY, PROGRESSIVE); and corticobasal degeneration.
Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
A generic term for any circumscribed mass of foreign (e.g., lead or viruses) or metabolically inactive materials (e.g., ceroid or MALLORY BODIES), within the cytoplasm or nucleus of a cell. Inclusion bodies are in cells infected with certain filtrable viruses, observed especially in nerve, epithelial, or endothelial cells. (Stedman, 25th ed)
Inherited disorders characterized by progressive atrophy and dysfunction of anatomically or physiologically related neurologic systems.
Disorders caused by imbalances in the protein homeostasis network - synthesis, folding, and transport of proteins; post-translational modifications; and degradation or clearance of misfolded proteins.
The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling.
Small proteinaceous infectious particles which resist inactivation by procedures that modify NUCLEIC ACIDS and contain an abnormal isoform of a cellular protein which is a major and necessary component. The abnormal (scrapie) isoform is PrPSc (PRPSC PROTEINS) and the cellular isoform PrPC (PRPC PROTEINS). The primary amino acid sequence of the two isoforms is identical. Human diseases caused by prions include CREUTZFELDT-JAKOB SYNDROME; GERSTMANN-STRAUSSLER SYNDROME; and INSOMNIA, FATAL FAMILIAL.
A group of genetic, infectious, or sporadic degenerative human and animal nervous system disorders associated with abnormal PRIONS. These diseases are characterized by conversion of the normal prion protein to an abnormal configuration via a post-translational process. In humans, these conditions generally feature DEMENTIA; ATAXIA; and a fatal outcome. Pathologic features include a spongiform encephalopathy without evidence of inflammation. The older literature occasionally refers to these as unconventional SLOW VIRUS DISEASES. (From Proc Natl Acad Sci USA 1998 Nov 10;95(23):13363-83)
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
A family of homologous proteins of low MOLECULAR WEIGHT that are predominately expressed in the BRAIN and that have been implicated in a variety of human diseases. They were originally isolated from CHOLINERGIC FIBERS of TORPEDO.
Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.
A group of dominantly inherited, predominately late-onset, cerebellar ataxias which have been divided into multiple subtypes based on clinical features and genetic mapping. Progressive ataxia is a central feature of these conditions, and in certain subtypes POLYNEUROPATHY; DYSARTHRIA; visual loss; and other disorders may develop. (From Joynt, Clinical Neurology, 1997, Ch65, pp 12-17; J Neuropathol Exp Neurol 1998 Jun;57(6):531-43)
Heterogeneous group of neurodegenerative disorders characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Multiple subtypes or forms are recognized based on presence or absence of TAU PROTEIN inclusions. FTLD includes three clinical syndromes: FRONTOTEMPORAL DEMENTIA, semantic dementia, and PRIMARY PROGRESSIVE NONFLUENT APHASIA.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
An increased number of contiguous trinucleotide repeats in the DNA sequence from one generation to the next. The presence of these regions is associated with diseases such as FRAGILE X SYNDROME and MYOTONIC DYSTROPHY. Some CHROMOSOME FRAGILE SITES are composed of sequences where trinucleotide repeat expansion occurs.
The most common clinical form of FRONTOTEMPORAL LOBAR DEGENERATION, this dementia presents with personality and behavioral changes often associated with disinhibition, apathy, and lack of insight.
An autosomal recessive disease, usually of childhood onset, characterized pathologically by degeneration of the spinocerebellar tracts, posterior columns, and to a lesser extent the corticospinal tracts. Clinical manifestations include GAIT ATAXIA, pes cavus, speech impairment, lateral curvature of spine, rhythmic head tremor, kyphoscoliosis, congestive heart failure (secondary to a cardiomyopathy), and lower extremity weakness. Most forms of this condition are associated with a mutation in a gene on chromosome 9, at band q13, which codes for the mitochondrial protein frataxin. (From Adams et al., Principles of Neurology, 6th ed, p1081; N Engl J Med 1996 Oct 17;335(16):1169-75) The severity of Friedreich ataxia associated with expansion of GAA repeats in the first intron of the frataxin gene correlates with the number of trinucleotide repeats. (From Durr et al, N Engl J Med 1996 Oct 17;335(16):1169-75)
Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)
The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.
A group of severe neurodegenerative diseases characterized by intracellular accumulation of autofluorescent wax-like lipid materials (CEROID; LIPOFUSCIN) in neurons. There are several subtypes based on mutations of the various genes, time of disease onset, and severity of the neurological defects such as progressive DEMENTIA; SEIZURES; and visual failure.
An island in Micronesia, east of the Philippines, the largest and southernmost of the Marianas. Its capital is Agana. It was discovered by Magellan in 1521 and occupied by Spain in 1565. They ceded it to the United States in 1898. It is an unincorporated territory of the United States, administered by the Department of the Interior since 1950. The derivation of the name Guam is in dispute. (From Webster's New Geographical Dictionary, 1988, p471)
A fibrous protein complex that consists of proteins folded into a specific cross beta-pleated sheet structure. This fibrillar structure has been found as an alternative folding pattern for a variety of functional proteins. Deposits of amyloid in the form of AMYLOID PLAQUES are associated with a variety of degenerative diseases. The amyloid structure has also been found in a number of functional proteins that are unrelated to disease.
The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.
An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness.
Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) UBIQUITINS. As one of the hallmarks of ALZHEIMER DISEASE, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease.
A neurodegenerative disease characterized by dementia, mild parkinsonism, and fluctuations in attention and alertness. The neuropsychiatric manifestations tend to precede the onset of bradykinesia, MUSCLE RIGIDITY, and other extrapyramidal signs. DELUSIONS and visual HALLUCINATIONS are relatively frequent in this condition. Histologic examination reveals LEWY BODIES in the CEREBRAL CORTEX and BRAIN STEM. SENILE PLAQUES and other pathologic features characteristic of ALZHEIMER DISEASE may also be present. (From Neurology 1997;48:376-380; Neurology 1996;47:1113-1124)
A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.
A group of disorders which feature impaired motor control characterized by bradykinesia, MUSCLE RIGIDITY; TREMOR; and postural instability. Parkinsonian diseases are generally divided into primary parkinsonism (see PARKINSON DISEASE), secondary parkinsonism (see PARKINSON DISEASE, SECONDARY) and inherited forms. These conditions are associated with dysfunction of dopaminergic or closely related motor integration neuronal pathways in the BASAL GANGLIA.
An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Intracytoplasmic, eosinophilic, round to elongated inclusions found in vacuoles of injured or fragmented neurons. The presence of Lewy bodies is the histological marker of the degenerative changes in LEWY BODY DISEASE and PARKINSON DISEASE but they may be seen in other neurological conditions. They are typically found in the substantia nigra and locus coeruleus but they are also seen in the basal forebrain, hypothalamic nuclei, and neocortex.
The directed transport of ORGANELLES and molecules along nerve cell AXONS. Transport can be anterograde (from the cell body) or retrograde (toward the cell body). (Alberts et al., Molecular Biology of the Cell, 3d ed, pG3)
The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.
Microsatellite repeats consisting of three nucleotides dispersed in the euchromatic arms of chromosomes.
Diseases characterized by a selective degeneration of the motor neurons of the spinal cord, brainstem, or motor cortex. Clinical subtypes are distinguished by the major site of degeneration. In AMYOTROPHIC LATERAL SCLEROSIS there is involvement of upper, lower, and brainstem motor neurons. In progressive muscular atrophy and related syndromes (see MUSCULAR ATROPHY, SPINAL) the motor neurons in the spinal cord are primarily affected. With progressive bulbar palsy (BULBAR PALSY, PROGRESSIVE), the initial degeneration occurs in the brainstem. In primary lateral sclerosis, the cortical neurons are affected in isolation. (Adams et al., Principles of Neurology, 6th ed, p1089)
A degenerative disease of the central nervous system characterized by balance difficulties; OCULAR MOTILITY DISORDERS (supranuclear ophthalmoplegia); DYSARTHRIA; swallowing difficulties; and axial DYSTONIA. Onset is usually in the fifth decade and disease progression occurs over several years. Pathologic findings include neurofibrillary degeneration and neuronal loss in the dorsal MESENCEPHALON; SUBTHALAMIC NUCLEUS; RED NUCLEUS; pallidum; dentate nucleus; and vestibular nuclei. (From Adams et al., Principles of Neurology, 6th ed, pp1076-7)
Diseases caused by abnormal function of the MITOCHONDRIA. They may be caused by mutations, acquired or inherited, in mitochondrial DNA or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes.
Neurons which activate MUSCLE CELLS.
A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell.
Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord.
A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.
A plant genus of the family Cycadaceae, order Cycadales, class Cycadopsida, division CYCADOPHYTA of palm-like trees. It is a source of CYCASIN, the beta-D-glucoside of methylazoxymethanol.
Proteins that specifically bind to IRON.
A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.
A group of disorders marked by progressive degeneration of motor neurons in the spinal cord resulting in weakness and muscular atrophy, usually without evidence of injury to the corticospinal tracts. Diseases in this category include Werdnig-Hoffmann disease and later onset SPINAL MUSCULAR ATROPHIES OF CHILDHOOD, most of which are hereditary. (Adams et al., Principles of Neurology, 6th ed, p1089)
The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulchi. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.
A rare form of DEMENTIA that is sometimes familial. Clinical features include APHASIA; APRAXIA; CONFUSION; ANOMIA; memory loss; and personality deterioration. This pattern is consistent with the pathologic findings of circumscribed atrophy of the poles of the FRONTAL LOBE and TEMPORAL LOBE. Neuronal loss is maximal in the HIPPOCAMPUS, entorhinal cortex, and AMYGDALA. Some ballooned cortical neurons contain argentophylic (Pick) bodies. (From Brain Pathol 1998 Apr;8(2):339-54; Adams et al., Principles of Neurology, 6th ed, pp1057-9)
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
A multifunctional heterogeneous-nuclear ribonucleoprotein that may play a role in homologous DNA pairing and recombination. The N-terminal portion of protein is a potent transcriptional activator, while the C terminus is required for RNA binding. The name FUS refers to the fact that genetic recombination events result in fusion oncogene proteins (ONCOGENE PROTEINS, FUSION) that contain the N-terminal region of this protein. These fusion proteins have been found in myxoid liposarcoma (LIPOSARCOMA, MYXOID) and acute myeloid leukemia.
The non-neuronal cells of the nervous system. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the BLOOD-BRAIN BARRIER and BLOOD-RETINAL BARRIER, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear.
The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.
Accumulations of extracellularly deposited AMYLOID FIBRILS within tissues.
Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
A syndrome complex composed of three conditions which represent clinical variants of the same disease process: STRIATONIGRAL DEGENERATION; SHY-DRAGER SYNDROME; and the sporadic form of OLIVOPONTOCEREBELLAR ATROPHIES. Clinical features include autonomic, cerebellar, and basal ganglia dysfunction. Pathologic examination reveals atrophy of the basal ganglia, cerebellum, pons, and medulla, with prominent loss of autonomic neurons in the brain stem and spinal cord. (From Adams et al., Principles of Neurology, 6th ed, p1076; Baillieres Clin Neurol 1997 Apr;6(1):187-204; Med Clin North Am 1999 Mar;83(2):381-92)
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
ANIMALS whose GENOME has been altered by GENETIC ENGINEERING, or their offspring.
The black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce DOPAMINE, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored MELANIN is a by-product of dopamine synthesis.
A family of cellular proteins that mediate the correct assembly or disassembly of polypeptides and their associated ligands. Although they take part in the assembly process, molecular chaperones are not components of the final structures.
Abnormal isoform of prion proteins (PRIONS) resulting from a posttranslational modification of the cellular prion protein (PRPC PROTEINS). PrPSc are disease-specific proteins seen in certain human and animal neurodegenerative diseases (PRION DISEASES).
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A synuclein that is closely related to ALPHA-SYNUCLEIN. It may play a neuroprotective role against some of the toxic effects of aggregated ALPHA-SYNUCLEIN.
A performance test based on forced MOTOR ACTIVITY on a rotating rod, usually by a rodent. Parameters include the riding time (seconds) or endurance. Test is used to evaluate balance and coordination of the subjects, particular in experimental animal models for neurological disorders and drug effects.
Conditions which feature clinical manifestations resembling primary Parkinson disease that are caused by a known or suspected condition. Examples include parkinsonism caused by vascular injury, drugs, trauma, toxin exposure, neoplasms, infections and degenerative or hereditary conditions. Clinical features may include bradykinesia, rigidity, parkinsonian gait, and masked facies. In general, tremor is less prominent in secondary parkinsonism than in the primary form. (From Joynt, Clinical Neurology, 1998, Ch38, pp39-42)
Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.
Circumscribed masses of foreign or metabolically inactive materials, within the CELL NUCLEUS. Some are VIRAL INCLUSION BODIES.
An increase number of repeats of a genomic, tandemly repeated DNA sequence from one generation to the next.
A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.
Neurons whose primary neurotransmitter is DOPAMINE.
Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.
Diseases characterized by the presence of abnormally phosphorylated, ubiquitinated, and cleaved DNA-binding protein TDP-43 in affected brain and spinal cord. Inclusions of the pathologic protein in neurons and glia, without the presence of AMYLOID, is the major feature of these conditions, thus making these proteinopathies distinct from most other neurogenerative disorders in which protein misfolding leads to brain amyloidosis. Both frontotemporal lobar degeneration and AMYOTROPHIC LATERAL SCLEROSIS exhibit this common method of pathogenesis and thus they may represent two extremes of a continuous clinicopathological spectrum of one disease.
Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues.
A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Type III intermediate filament proteins that assemble into neurofilaments, the major cytoskeletal element in nerve axons and dendrites. They consist of three distinct polypeptides, the neurofilament triplet. Types I, II, and IV intermediate filament proteins form other cytoskeletal elements such as keratins and lamins. It appears that the metabolism of neurofilaments is disturbed in Alzheimer's disease, as indicated by the presence of neurofilament epitopes in the neurofibrillary tangles, as well as by the severe reduction of the expression of the gene for the light neurofilament subunit of the neurofilament triplet in brains of Alzheimer's patients. (Can J Neurol Sci 1990 Aug;17(3):302)
A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES.
A nonspecific term referring both to the pathologic finding of swelling of distal portions of axons in the brain and to disorders which feature this finding. Neuroaxonal dystrophy is seen in various genetic diseases, vitamin deficiencies, and aging. Infantile neuroaxonal dystrophy is an autosomal recessive disease characterized by arrested psychomotor development at 6 months to 2 years of age, ataxia, brain stem dysfunction, and quadriparesis. Juvenile and adult forms also occur. Pathologic findings include brain atrophy and widespread accumulation of axonal spheroids throughout the neuroaxis, peripheral nerves, and dental pulp. (From Davis & Robertson, Textbook of Neuropathology, 2nd ed, p927)
Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or PERIPHERAL NERVE DISEASES. Motor ataxia may be associated with CEREBELLAR DISEASES; CEREBRAL CORTEX diseases; THALAMIC DISEASES; BASAL GANGLIA DISEASES; injury to the RED NUCLEUS; and other conditions.
Established cell cultures that have the potential to propagate indefinitely.
Inflammation of the BRAIN due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see ENCEPHALITIS, VIRAL) are a relatively frequent cause of this condition.
Normal cellular isoform of prion proteins (PRIONS) encoded by a chromosomal gene and found in normal and scrapie-infected brain tissue, and other normal tissue. PrPC are protease-sensitive proteins whose function is unknown. Posttranslational modification of PrPC into PrPSC leads to infectivity.
Traumatic injuries to the brain, cranial nerves, spinal cord, autonomic nervous system, or neuromuscular system, including iatrogenic injuries induced by surgical procedures.
A rare transmissible encephalopathy most prevalent between the ages of 50 and 70 years. Affected individuals may present with sleep disturbances, personality changes, ATAXIA; APHASIA, visual loss, weakness, muscle atrophy, MYOCLONUS, progressive dementia, and death within one year of disease onset. A familial form exhibiting autosomal dominant inheritance and a new variant CJD (potentially associated with ENCEPHALOPATHY, BOVINE SPONGIFORM) have been described. Pathological features include prominent cerebellar and cerebral cortical spongiform degeneration and the presence of PRIONS. (From N Engl J Med, 1998 Dec 31;339(27))
The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
An intermediate filament protein found only in glial cells or cells of glial origin. MW 51,000.
A dominantly-inherited ATAXIA first described in people of Azorean and Portuguese descent, and subsequently identified in Brazil, Japan, China, and Australia. This disorder is classified as one of the SPINOCEREBELLAR ATAXIAS (Type 3) and has been associated with a mutation of the MJD1 gene on chromosome 14. Clinical features include progressive ataxia, DYSARTHRIA, postural instability, nystagmus, eyelid retraction, and facial FASCICULATIONS. DYSTONIA is prominent in younger patients (referred to as Type I Machado-Joseph Disease). Type II features ataxia and ocular signs; Type III features MUSCULAR ATROPHY and a sensorimotor neuropathy; and Type IV features extrapyramidal signs combined with a sensorimotor neuropathy. (From Clin Neurosci 1995;3(1):17-22; Ann Neurol 1998 Mar;43(3):288-96)
A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured. Such rupture is supposed to be under metabolic (hormonal) control. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
Compounds having the nitro group, -NO2, attached to carbon. When attached to nitrogen they are nitramines and attached to oxygen they are NITRATES.
Proteins that form the core of amyloid fibrils. For example, the core of amyloid A is formed from amyloid A protein, also known as serum amyloid A protein or SAA protein.
One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.
An active neurotoxic metabolite of 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE. The compound reduces dopamine levels, inhibits the biosynthesis of catecholamines, depletes cardiac norepinephrine and inactivates tyrosine hydroxylase. These and other toxic effects lead to cessation of oxidative phosphorylation, ATP depletion, and cell death. The compound, which is related to PARAQUAT, has also been used as an herbicide.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Formation of NEURONS which involves the differentiation and division of STEM CELLS in which one or both of the daughter cells become neurons.
Disturbances in mental processes related to learning, thinking, reasoning, and judgment.
Biphasic dose responses of cells or organisms (including microorganisms) to an exogenous or intrinsic factor, in which the factor induces stimulatory or beneficial effects at low doses and inhibitory or adverse effects at high doses.
Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.
A heterogenous group of degenerative syndromes marked by progressive cerebellar dysfunction either in isolation or combined with other neurologic manifestations. Sporadic and inherited subtypes occur. Inheritance patterns include autosomal dominant, autosomal recessive, and X-linked.
Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.
Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques.
A fatal disease of the nervous system in sheep and goats, characterized by pruritus, debility, and locomotor incoordination. It is caused by proteinaceous infectious particles called PRIONS.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Degeneration of distal aspects of a nerve axon following injury to the cell body or proximal portion of the axon. The process is characterized by fragmentation of the axon and its MYELIN SHEATH.
A homolog of ALPHA-SYNUCLEIN that plays a role in neurofilament network integrity. It is overexpressed in a variety of human NEOPLASMS and may be involved in modulating AXON architecture during EMBRYONIC DEVELOPMENT and in the adult. Gamma-Synuclein may also activate SIGNAL TRANSDUCTION PATHWAYS associated with ETS-DOMAIN PROTEIN ELK-1.
A dopaminergic neurotoxic compound which produces irreversible clinical, chemical, and pathological alterations that mimic those found in Parkinson disease.
Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.
A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.
Proteins produced from GENES that have acquired MUTATIONS.
High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.
Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
A neurotransmitter analogue that depletes noradrenergic stores in nerve endings and induces a reduction of dopamine levels in the brain. Its mechanism of action is related to the production of cytolytic free-radicals.
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
An autosomal recessive lipid storage disorder that is characterized by accumulation of CHOLESTEROL and SPHINGOMYELINS in cells of the VISCERA and the CENTRAL NERVOUS SYSTEM. Type C (or C1) and type D are allelic disorders caused by mutation of gene (NPC1) encoding a protein that mediate intracellular cholesterol transport from lysosomes. Clinical signs include hepatosplenomegaly and chronic neurological symptoms. Type D is a variant in people with a Nova Scotia ancestry.
Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Peptide hydrolases that contain at the active site a SERINE residue involved in catalysis.
A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.
An autosomal dominant disorder characterized by degeneration of the THALAMUS and progressive insomnia. It is caused by a mutation in the prion protein (PRIONS).
A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.
A member of the nerve growth factor family of trophic factors. In the brain BDNF has a trophic action on retinal, cholinergic, and dopaminergic neurons, and in the peripheral nervous system it acts on both motor and sensory neurons. (From Kendrew, The Encyclopedia of Molecular Biology, 1994)
Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
The continuous remodeling of MITOCHONDRIA shape by fission and fusion in response to physiological conditions.
The use of silver, usually silver nitrate, as a reagent for producing contrast or coloration in tissue specimens.
A botanical insecticide that is an inhibitor of mitochondrial electron transport.
A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.
The observable response an animal makes to any situation.
Elements of limited time intervals, contributing to particular results or situations.
A group of inherited diseases that share similar phenotypes but are genetically diverse. Different genetic loci for autosomal recessive, autosomal dominant, and x-linked forms of hereditary spastic paraplegia have been identified. Clinically, patients present with slowly progressive distal limb weakness and lower extremity spasticity. Peripheral sensory neurons may be affected in the later stages of the disease. (J Neurol Neurosurg Psychiatry 1998 Jan;64(1):61-6; Curr Opin Neurol 1997 Aug;10(4):313-8)
The process by which chemical compounds provide protection to cells against harmful agents.
The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Self-renewing cells that generate the main phenotypes of the nervous system in both the embryo and adult. Neural stem cells are precursors to both NEURONS and NEUROGLIA.
Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.
Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.
The physical activity of a human or an animal as a behavioral phenomenon.
The output neurons of the cerebellar cortex.
A condition caused by the neurotoxin MPTP which causes selective destruction of nigrostriatal dopaminergic neurons. Clinical features include irreversible parkinsonian signs including rigidity and bradykinesia (PARKINSON DISEASE, SECONDARY). MPTP toxicity is also used as an animal model for the study of PARKINSON DISEASE. (Adams et al., Principles of Neurology, 6th ed, p1072; Neurology 1986 Feb;36(2):250-8)
The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.
A state in which attention is largely directed inward upon one's self.
A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)
A subclass of histone deacetylases that are NAD-dependent. Several members of the SIRTUINS family are included in this subclass.
Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.
The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A species of fruit fly much used in genetics because of the large size of its chromosomes.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.
The middle of the three primitive cerebral vesicles of the embryonic brain. Without further subdivision, midbrain develops into a short, constricted portion connecting the PONS and the DIENCEPHALON. Midbrain contains two major parts, the dorsal TECTUM MESENCEPHALI and the ventral TEGMENTUM MESENCEPHALI, housing components of auditory, visual, and other sensorimoter systems.
In tissue culture, hairlike projections of neurons stimulated by growth factors and other molecules. These projections may go on to form a branched tree of dendrites or a single axon or they may be reabsorbed at a later stage of development. "Neurite" may refer to any filamentous or pointed outgrowth of an embryonal or tissue-culture neural cell.
Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury.
A metabolite of tryptophan with a possible role in neurodegenerative disorders. Elevated CSF levels of quinolinic acid are correlated with the severity of neuropsychological deficits in patients who have AIDS.
A division of GYMNOSPERMS which look like palm trees (ARECACEAE) but are more closely related to PINUS. They have large cones and large pinnate leaves and are sometimes called cycads, a term which may also refer more narrowly to cycadales or CYCAS.
A species of nematode that is widely used in biological, biochemical, and genetic studies.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
The transfer of STEM CELLS from one individual to another within the same species (TRANSPLANTATION, HOMOLOGOUS) or between species (XENOTRANSPLANTATION), or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). The source and location of the stem cells determines their potency or pluripotency to differentiate into various cell types.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC
A class of large neuroglial (macroglial) cells in the central nervous system. Oligodendroglia may be called interfascicular, perivascular, or perineuronal (not the same as SATELLITE CELLS, PERINEURONAL of GANGLIA) according to their location. They form the insulating MYELIN SHEATH of axons in the central nervous system.
A progressive form of dementia characterized by the global loss of language abilities and initial preservation of other cognitive functions. Fluent and nonfluent subtypes have been described. Eventually a pattern of global cognitive dysfunction, similar to ALZHEIMER DISEASE, emerges. Pathologically, there are no Alzheimer or PICK DISEASE like changes, however, spongiform changes of cortical layers II and III are present in the TEMPORAL LOBE and FRONTAL LOBE. (From Brain 1998 Jan;121(Pt 1):115-26)
A heterogeneous group of primarily familial disorders characterized by myoclonic seizures, tonic-clonic seizures, ataxia, progressive intellectual deterioration, and neuronal degeneration. These include LAFORA DISEASE; MERRF SYNDROME; NEURONAL CEROID-LIPOFUSCINOSIS; sialidosis (see MUCOLIPIDOSES), and UNVERRICHT-LUNDBORG SYNDROME.
A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN.
Mice which carry mutant genes for neurologic defects or abnormalities.
The biochemical and electrophysiological interactions between the NERVOUS SYSTEM and IMMUNE SYSTEM.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A class of MOLECULAR CHAPERONES found in both prokaryotes and in several compartments of eukaryotic cells. These proteins can interact with polypeptides during a variety of assembly processes in such a way as to prevent the formation of nonfunctional structures.
A general term indicating inflammation of a peripheral or cranial nerve. Clinical manifestation may include PAIN; PARESTHESIAS; PARESIS; or HYPESTHESIA.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
The entire nerve apparatus, composed of a central part, the brain and spinal cord, and a peripheral part, the cranial and spinal nerves, autonomic ganglia, and plexuses. (Stedman, 26th ed)

Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? (1/2534)

Brain-derived neurotrophic factor (BDNF) has potent effects on neuronal survival and plasticity during development and after injury. In the nervous system, neurons are considered the major cellular source of BDNF. We demonstrate here that in addition, activated human T cells, B cells, and monocytes secrete bioactive BDNF in vitro. Notably, in T helper (Th)1- and Th2-type CD4(+) T cell lines specific for myelin autoantigens such as myelin basic protein or myelin oligodendrocyte glycoprotein, BDNF production is increased upon antigen stimulation. The BDNF secreted by immune cells is bioactive, as it supports neuronal survival in vitro. Using anti-BDNF monoclonal antibody and polyclonal antiserum, BDNF immunoreactivity is demonstrable in inflammatory infiltrates in the brain of patients with acute disseminated encephalitis and multiple sclerosis. The results raise the possibility that in the nervous system, inflammatory infiltrates have a neuroprotective effect, which may limit the success of nonselective immunotherapies.  (+info)

A new X linked neurodegenerative syndrome with mental retardation, blindness, convulsions, spasticity, mild hypomyelination, and early death maps to the pericentromeric region. (2/2534)

We report on a family with an X linked neurodegenerative disorder consisting of mental retardation, blindness, convulsions, spasticity, and early death. Neuropathological examination showed mild hypomyelination. By linkage analysis, the underlying genetic defect could be assigned to the pericentromeric region of the X chromosome with a maximum lod score of 3.30 at theta=0.0 for the DXS1204 locus with DXS337 and PGK1P1 as flanking markers.  (+info)

Increased neurodegeneration during ageing in mice lacking high-affinity nicotine receptors. (3/2534)

We have examined neuroanatomical, biochemical and endocrine parameters and spatial learning in mice lacking the beta2 subunit of the nicotinic acetylcholine receptor (nAChR) during ageing. Aged beta2(-/-) mutant mice showed region-specific alterations in cortical regions, including neocortical hypotrophy, loss of hippocampal pyramidal neurons, astro- and microgliosis and elevation of serum corticosterone levels. Whereas adult mutant and control animals performed well in the Morris maze, 22- to 24-month-old beta2(-/-) mice were significantly impaired in spatial learning. These data show that beta2 subunit-containing nAChRs can contribute to both neuronal survival and maintenance of cognitive performance during ageing. beta2(-/-) mice may thus serve as one possible animal model for some of the cognitive deficits and degenerative processes which take place during physiological ageing and in Alzheimer's disease, particularly those associated with dysfunction of the cholinergic system.  (+info)

Mitochondria in organismal aging and degeneration. (4/2534)

Several lines of experimentation support the view that the genetic, biochemical and bioenergetic functions of somatic mitochondria deteriorate during normal aging. Deletion mutations of the mitochondrial genome accumulate exponentially with age in nerve and muscle tissue of humans and multiple other species. In muscle, a tissue that undergoes age-related fiber loss and atrophy in humans, there is an exponential rise in the number of cytochrome-oxidase-deficient fibers, which is first detectable in the fourth decile of age. Most biochemical studies of animal mitochondrial activity indicate a decline in electron transport activity with age, as well as decreased bioenergetic capacity with age, as measured by mitochondrial membrane potential. Mitochondrial mutations may be both the result of mitochondrial oxidative stress, and cells bearing pure populations of pathogenic mitochondrial mutations are sensitized to oxidant stress. Oxidant stress to mitochondria is known to induce the mitochondrial permeability transition, which has recently been implicated in the release of cytochrome c and the initiation of apoptosis. Thus several lines of evidence support a contribution of mitochondrial dysfunction to the phenotypic changes associated with aging.  (+info)

Apoptosis in neurodegenerative diseases: the role of mitochondria. (5/2534)

Nerve cell death is the central feature of the human neurodegenerative diseases. It has long been thought that nerve cell death in these disorders occurs by way of necrosis, a process characterized by massive transmembrane ion currents, compromise of mitochondrial ATP production, and the formation of high levels of reactive oxygen species combining to induce rapid disruption of organelles, cell swelling, and plasma membrane rupture with a secondary inflammatory response. Nuclear DNA is relatively preserved. Recent evidence now indicates that the process of apoptosis rather than necrosis primarily contributes to nerve cell death in neurodegeneration. This has opened up new avenues for understanding the pathogenesis of neurodegeneration and may lead to new and more effective therapeutic approaches to these diseases.  (+info)

Nitric oxide, mitochondria and neurological disease. (6/2534)

Damage to the mitochondrial electron transport chain has been suggested to be an important factor in the pathogenesis of a range of neurological disorders, such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, stroke and amyotrophic lateral sclerosis. There is also a growing body of evidence to implicate excessive or inappropriate generation of nitric oxide (NO) in these disorders. It is now well documented that NO and its toxic metabolite, peroxynitrite (ONOO-), can inhibit components of the mitochondrial respiratory chain leading, if damage is severe enough, to a cellular energy deficiency state. Within the brain, the susceptibility of different brain cell types to NO and ONOO- exposure may be dependent on factors such as the intracellular reduced glutathione (GSH) concentration and an ability to increase glycolytic flux in the face of mitochondrial damage. Thus neurones, in contrast to astrocytes, appear particularly vulnerable to the action of these molecules. Following cytokine exposure, astrocytes can increase NO generation, due to de novo synthesis of the inducible form of nitric oxide synthase (NOS). Whilst the NO/ONOO- so formed may not affect astrocyte survival, these molecules may diffuse out to cause mitochondrial damage, and possibly cell death, to other cells, such as neurones, in close proximity. Evidence is now available to support this scenario for neurological disorders, such as multiple sclerosis. In other conditions, such as ischaemia, increased availability of glutamate may lead to an activation of a calcium-dependent nitric oxide synthase associated with neurones. Such increased/inappropriate NO formation may contribute to energy depletion and neuronal cell death. The evidence available for NO/ONOO--mediated mitochondrial damage in various neurological disorders is considered and potential therapeutic strategies are proposed.  (+info)

Studies on the role of dopamine in the degeneration of 5-HT nerve endings in the brain of Dark Agouti rats following 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') administration. (7/2534)

1. We investigated whether dopamine plays a role in the neurodegeneration of 5-hydroxytryptamine (5-HT) nerve endings occurring in Dark Agouti rat brain after 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') administration. 2. Haloperidol (2 mg kg(-1) i.p.) injected 5 min prior and 55 min post MDMA (15 mg kg(-1) i.p.) abolished the acute MDMA-induced hyperthermia and attenuated the neurotoxic loss of 5-HT 7 days later. When the rectal temperature of MDMA + haloperidol treated rats was kept elevated, this protective effect was marginal. 3. MDMA (15 mg kg(-1)) increased the dopamine concentration in the dialysate from a striatal microdialysis probe by 800%. L-DOPA (25 mg kg(-1) i.p., plus benserazide, 6.25 mg kg(-1) i.p.) injected 2 h after MDMA (15 mg kg(-1)) enhanced the increase in dopamine in the dialysate, but subsequent neurodegeneration was unaltered. L-DOPA (25 mg kg(-1)) injected before a sub-toxic dose of MDMA (5 mg kg(-1)) failed to induce neurodegeneration. 4. The MDMA-induced increase in free radical formation in the hippocampus (indicated by increased 2,3- and 2,5-dihydroxybenzoic acid in a microdialysis probe perfused with salicylic acid) was unaltered by L-DOPA. 5. The neuroprotective drug clomethiazole (50 mg kg(-1) i.p.) did not influence the MDMA-induced increase in extracellular dopamine. 6. These data suggest that previous observations on the protective effect of haloperidol and potentiating effect of L-DOPA on MDMA-induced neurodegeneration may have resulted from effects on MDMA-induced hyperthermia. 7. The increased extracellular dopamine concentration following MDMA may result from effects of MDMA on dopamine re-uptake, monoamine oxidase and 5-HT release rather than an 'amphetamine-like' action on dopamine release, thus explaining why the drug does not induce degeneration of dopamine nerve endings.  (+info)

Possible role of NF-kappaB and p53 in the glutamate-induced pro-apoptotic neuronal pathway. (8/2534)

Apoptosis is now recognized as an important component in many progressive and acute neurodegenerative diseases. Extracellular signals and intracellular mechanisms triggering and regulating apoptosis in neuronal cells are still a matter of investigation. Here we review data from our and other laboratories with the aim to elucidate the nature of some proteins which are known to be involved in cell cycle regulation as well as in promoting degeneration and apoptosis of neurons. The following molecules will be taken into consideration: NF-kappaB, p53, p21 and MSH2. These proteins are activated by neurotoxic experimental conditions which involve the stimulation of selective receptors for the excitatory aminoacid glutamate. Thus, we hypothesize their contribution to an intracellular pathway responsible for the glutamate-induced neuronal death. Identification of such mechanisms could be relevant for understanding the apoptosis associated with various neurodegenerative diseases as well as for developing novel strategies of pharmacological intervention.  (+info)

The EU Joint Programme - Neurodegenerative Disease Research (JPND) initiative launched a new joint transnational call for multinational research projects on personalised medicine for neurodegenerative diseases. The call is launched in partnership with the European Commission and has a budget of ca. EUR 30 M.. Neurodegenerative diseases are debilitating and still largely untreatable conditions. They are characterised by a large variability in their origins, mechanisms and clinical expression. When searching for a medical solution, e.g. a treatment or an optimised approach for care, this large variability constitutes a major hurdle if not controlled. Indeed a treatment addressing one disease pathway may not be useful for all patients experiencing the relevant symptoms. Thus, one of the greatest challenges for treating neurodegenerative diseases is the deciphering of this variability.. The following neurodegenerative diseases are included in the call:. ...
Neitzel, J.; Watts, M.; Diehl-Schmid, J.; Ortner, M.; Grimmer, T.; Yakushev, I.; Bublak, P.; Preul, C.; Finke, K.; Sorg, C. (2016): Distinct subcortical atrophy patterns across four different neurodegenerative syndromes. In: Journal of Neurochemistry, Vol. 138: p. 385 ...
The human APOE gene, which codes for apolipoprotein E (apoE), has three major polymorphic alleles: ε2, ε3, and ε4 that give rise to amino acid substitutions. APOE-ε4 is a strong risk factor of sporadic Alzheimers disease (AD) but the reason why is still unknown despite intense research for more than 20 years. The aim of the study was to investigate if the concentrations of total apoE and the specific apoE isoforms in cerebrospinal fluid (CSF) differ between various neurodegenerative diseases and control individuals, as well as among the APOE genotypes. Quantification of total apoE and specific apoE isoforms (E2, E3, and E4) in CSF was performed using high-resolution parallel reaction monitoring mass spectrometry. In total, 1820 individuals were involved in the study including clinically diagnosed AD patients (n = 228), cognitively unimpaired (CU) patients (n = 896), and patients with other neurodegenerative disorders (n = 696). Follow-up data was available for 100 individuals, assessed at two time
Aggregation of misfolded proteins and the associated loss of neurons are considered as a hallmark of numerous neurodegenerative diseases. Optineurin is present in protein inclusions observed in various neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Huntingtons disease, Alzheimers disease, Parkinsons disease, Creutzfeld-Jacob disease and Picks disease. Optineurin deletion mutations have also been described in ALS patients. However, the role of optineurin in mechanisms of protein aggregation remains unclear. In this report, we demonstrate that optineurin recognized various protein aggregates via its C-terminal coiled-coil domain in a ubiquitin-independent manner. We also show that optineurin depletion significantly increase protein aggregation in HeLa cells and morpholino-silencing of the optineurin ortholog in zebrafish causes the motor axonopathy phenotype similar to a zebrafish model of ALS. A more severe phenotype is observed when optineurin is depleted in ...
Abstract Platelets play an important role in a variety of disorders viz; cardiovascular, psychosomatic, psychiatric, thrombosis, HIV/AIDS in addition to various neurodegenerative diseases (NDD). Recent evidence indicates that platelet react to divers
BACKGROUND & OBJECTIVE: Alzheimers disease (AD) and Parkinsons disease (PD) affect an increasing number of the elderly population worldwide. The existing treatments mainly improve the core symptoms of AD and PD in a temporary manner and cause alarming side effects. Naturally occurring flavonoids are well-documented for neuroprotective and neurorestorative effects against various neurodegenerative diseases. Thus, we analyzed the pharmacokinetics of eight potent natural products flavonoids for the druggability and discussed the neuroprotective and neurorestorative effects and the underlying mechanisms. CONCLUSION: This review provides valuable clues for the development of novel therapeutics against neurodegenerative diseases ...
Neurodegenerative diseases are among the most common causes of disability worldwide. Although neurodegenerative diseases are heterogeneous in both their clinical features and the underlying physiology, they are all characterised by progressive loss of specific neuronal populations. Recent experiment …
This book sheds new light on neurodegenerative disorders as systemic diseases. Classically, neuronal cell death was a hallmark of such disorders. However, it has become evident that neural dysfunction is more important in the pathophysiology of neurodegenerative disorders. More recently, the prionoid-spreading hypothesis of disease-causing molecules has attracted a great deal of attention. Therapeutic strategies thus must be reconsidered in the light that neurodegenerative disorders are indeed systemic diseases. The first part of this book introduces the concept of neurodegeneration in biology and pathophysiology. The second part focuses on clinical evaluation and biomarkers from the perspective of this new concept, while the third summarizes the risk factors of neurodegeneration. The fourth part of this work indicates future directions of treatment, and the final part discusses health promotion for prevention and quality of life. This book will be of interest to both researchers and medical ...
Neurodegenerative diseases affect millions of people worldwide, and Alzheimers disease and Parkinsons disease are the most common types. The risk of being affected by a neurodegenerative disease increases dramatically with age and despite substantial research and development investments, effective therapeutics for the millions of patients with neurodegenerative diseases remain elusive. This creates a critical need to improve our understanding of what causes neurodegenerative diseases and develop new approaches for treatment and prevention.. USC is uniquely positioned as one of the top research institutions in the nation with comprehensive neurodegenerative disease research capabilities from bench to bedside and back. USC is comprised of leading scientists contributing to better understanding of the pathogenesis and treatment of neurological disorders such as Alzheimers disease and stroke, and leading experts in big data neuro-informatics, neuroimaging, structure-based drug discovery, systems ...
Neurodegenerative diseases affect millions of people worldwide, and Alzheimers disease and Parkinsons disease are the most common types. More than five million Americans are living with Alzheimers disease, and at least 500,000 Americans live with Parkinsons disease, although some estimates are much higher.. Neurodegenerative diseases occur when nerve cells in the brain or peripheral nervous system lose function over time and ultimately die. Although treatments may help relieve some of the physical or mental symptoms associated with neurodegenerative diseases, there is currently no cure or way to slow disease progression.. The risk of being affected by a neurodegenerative disease increases dramatically with age. Population-wide health improvements have increased lifespan, which along with a larger generation of aging Americans means more people may be affected by neurodegenerative diseases in coming decades. This creates a critical need to improve our understanding of what causes ...
Living cells continually generate reactive oxygen species (ROS) through the respiratory chain during energetic metabolism. ROS at low or moderate concentration can play important physiological roles. However, an excessive amount of ROS under oxidative stress would be extremely deleterious. The central nervous system (CNS) is particularly vulnerable to oxidative stress due to its high oxygen consumption, weakly antioxidative systems and the terminal-differentiation characteristic of neurons. Thus, oxidative stress elicits various neurodegenerative diseases. In addition, chemotherapy could result in severe side effects on the CNS and peripheral nervous system (PNS) of cancer patients, and a growing body of evidence demonstrates the involvement of ROS in drug-induced neurotoxicities as well. Therefore, development of antioxidants as neuroprotective drugs is a potentially beneficial strategy for clinical therapy. In this review, we summarize the source, balance maintenance and physiologic functions of ROS,
Functional and structural connectivity measures, as assessed by means of functional and diffusion MRI, are emerging as potential intermediate biomarkers for Alzheimer disease (AD) and other disorders. This Review aims to summarize current evidence that connectivity biomarkers are associated with upstream and downstream disease processes (molecular pathology and clinical symptoms, respectively) in the major neurodegenerative diseases. The vast majority of studies have addressed functional and structural connectivity correlates of clinical phenotypes, confirming the predictable correlation with topography and disease severity in AD and frontotemporal dementia. In neurodegenerative diseases with motor symptoms, structural--but, to date, not functional--connectivity has been consistently found to be associated with clinical phenotype and disease severity. In the latest studies, the focus has moved towards the investigation of connectivity correlates of molecular pathology. Studies in cognitively healthy
ApoE is the main lipid-carrier protein in the brain and has a role in the transport and metabolism of many lipid classes. This is important because the brain is a fatty, lipid-rich organ. ApoE can take three different forms, and the consequences of these differences can profoundly affect processes like lipid homeostasis and neurodegeneration. One specific form, ApoE4, increases ones risk of developing Alzheimers by as much as eightfold. A recent thematic review series in the Journal of Lipid Research includes eight articles that explore the connections between brain lipids, ApoE and Alzheimers disease.. Lipid abnormalities are closely associated with various neurodegenerative diseases, said Ta-Yuan T.Y. Chang of Geisel School of Medicine at Dartmouth College. He and wife Catherine Chang have been researching cholesterol metabolism and its relationship to neurodegenerative diseases for more than four decades. As the coordinators of the series, they selected experts in their fields to ...
In a large multi-site study, the researchers identified more than 1,500 potential biomarkers in cerebrospinal fluid from patients with one of three neurodegenerative diseases: Alzheimers, Parksinsons, or dementia with Lewy bodies (DLB). Researchers identified different sets of potential biomarkers corresponding to each disease; each of the proteins are linked specifically to one of the diseases. The results appear in the new issue of the Journal of Alzheimers Disease.. Were getting very close to being able to use these biomarkers for the clinical diagnosis of Alzheimers and Parkinsons disease, and dementia with Lewy bodies, said the studys lead author, Dr. Jing Zhang, associate professor of pathology at the UW. His lab is at Harborview Medical Center. This is a major improvement on other biomarker detection techniques.. Alzheimers, Parkinsons, and other neurodegenerative diseases affect millions of people in the United States, and the toll of the diseases is expected to worsen as ...
Defects in kinesin-3 transport have been implicated in diverse genetic, developmental, neurodegenerative and cancer diseases. Despite their widespread functions and clinical importance, the mechanisms of kinesin-3 mediated intracellular transport, regulations and their deficiencies in the context of human diseases are largely unknown. The project will continue to investigating the members of this family at cellular, molecular, structural and single molecule level to gain fundamental insights into molecular mechanisms of neuronal transport systems and the implications for various neurodegenerative diseases caused by the defects in microtubule based transport system. We will use cultured hippocampal neurons and Caenorhabditis elegans as model systems ...
This programme of research is aimed at studying underlying mechanisms and treatments for the major neurodegenerative diseases - Alzheimers, Epilepsy, Parkinsons, and Huntingtons. Neurodegenerative diseases affect over 100,000 New Zealanders and this will markedly increase as the population ages.
The new research suggests that the cells may die because of naturally occurring gene variation in brain cells that were, until recently, assumed to be genetically identical. This variation - called somatic mosaicism - could explain why neurons in the temporal lobe are the first to die in Alzheimers, for example, and why dopaminergic neurons are the first to die in Parkinsons.. This has been a big open question in neuroscience, particularly in various neurodegenerative diseases, said neuroscientist Michael McConnell, PhD, of UVAs Center for Brain Immunology and Glia (BIG). What is this selective vulnerability? What underlies it? And so now, with our work, the hypotheses moving forward are that it could be that different regions of the brain actually have a different garden of these [variations] in young individuals and that sets up different regions for decline later in life.. A Most Unexpected Outcome. The finding emerged unexpectedly from McConnells investigations into schizophrenia. ...
This section examines evidence for neurovascular changes during normal ageing and for neurovascular and/or BBB dysfunction in various neurodegenerative diseases, as well as the possibility that vascular defects can precede neuronal changes.. Age-associated neurovascular changes. Normal ageing diminishes brain circulatory functions, including a detectable decay of CBF in the limbic and association cortices that has been suggested to underlie age-related cognitive changes77. Alterations in the cerebral microvasculature, but not changes in neural activity, have been shown to lead to age-dependent reductions in functional hyperaemia in the visual system in cats78 and in the sensorimotor cortex in pericyte-deficient mice33. Importantly, a recent longitudinal CBF study in neurologically normal individuals revealed that people bearing the apolipoprotein E (APOE) ɛ4allele - the major genetic risk factor for late-onset Alzheimers disease79, 80, 81 - showed greater regional CBF decline in brain regions ...
p,Striatal interneurons display a morphological and chemical heterogeneity that has been particularly well characterized in rats, monkeys and humans. By comparison much less is known of striatal interneurons in mice, although these animals are now widely used as transgenic models of various neurodegenerative diseases. The present immunohistochemical study aimed at characterizing striatal interneurons expressing calretinin (CR) in mice compared to those in squirrel monkeys and humans. The mouse striatum contains both small (9-12 μm) and medium-sized (15-20 μm) CR+ cells. The small cells are intensely stained with a single, slightly varicose and moderately arborized process. They occur throughout the striatum (77±9 cells/mm(3)), but prevail in the area of the subventricular zone and subcallosal streak, with statistically significant anteroposterior and dorsoventral decreasing gradients. The medium-sized cells are less intensely immunoreactive and possess 2-3 long, slightly varicose and poorly ...
Thanks in large part to the seminal work of Steve White and his colleagues, we appreciate the ordered complexity of the lipid bilayer and how it impacts the incorporation of integral membrane proteins as well as more peripherally associated proteins. Steves work also provides a vital foundation to tackle another challenge: cytotoxic oligomeric complexes which accumulate in various neurodegenerative diseases. These oligomers have a relatively fluid structure and interact with many different proteins in the cell, but their main target is thought to be the phospholipid membrane, either the plasma membrane or internal organelles such as the mitochondria. This fascinating encounter between two essentially fluid phases generates a more disordered membrane, and presumably promotes uncontrolled transport of small metal ions across the membrane barrier. Happily, this unwanted interaction may be suppressed by mobilizing the phospholipid bilayer into its own defense. Extruded nanolipoparticles (NLPs) ...
Title: Cannabinoids and Neurodegenerative Diseases. VOLUME: 8 ISSUE: 6. Author(s):Julian Romero and Jose Martinez-Orgado. Affiliation:Laboratorio de Investigacion, Hospital Universitario Fundacion Alcorcon and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), C/o Budapest 1, 28922, Alcorcon, Spain.. Keywords:Alzheimers disease, ischemia, neuroprotection, glia. Abstract: Although significant advances have taken place in recent years on our understanding of the molecular mechanisms of different neurodegenerative diseases, its translation into effective therapeutic treatments has not been as successful as could be expected. There is still a dramatic lack of curative treatments for the most frequent disorders and only symptomatic relief for many others. Under this perspective, the search for novel therapeutic approaches is demanding and significant attention and efforts have been directed to studying additional neurotransmission systems including the ...
Lou Gehrigs disease, known as amyotrophic lateral sclerosis or ALS, strikes healthy, middle-aged people seemingly at random. Of the major neurodegenerative diseases, it has the least hope for treatment and survival. Although mental capabilities stay intact, ALS paralyzes people,....... ...
Neurological disorders have a strong negative impact on the quality of life of affected patients, their close relatives as well as on the health economic system. Early diagnosis associated with better treatment outcomes remain difficult to reach. Similarly, misdiagnosis is frequent and can lead to the delivery of the wrong treatment to the patient. As a matter of fact, the therapeutic strategies developed to treat Alzheimers Disease (AD) and Parkinsons Disease (PD), two major neurodegenerative diseases, are unfortunately only effective for reducing the symptoms. This illustrates the lack of complete understanding of the mechanisms underlining neurodegeneration. In this context, this thesis aims to contribute to a precise comprehension of the synaptic transmission, at the cellular level, by providing a biocompatible brain interface capable of collecting neurochemicals while establishing a tight electrical connection with the cerebral tissues. The first part of this thesis deals with the design ...
Lou Gehrigs disease, known as amyotrophic lateral sclerosis or ALS, strikes healthy, middle-aged people seemingly at random. Of the major neurodegenerative diseases, it has the least hope for treatment and survival. Although mental capabilities stay intact, ALS paralyzes people,....... ...
DESCRIPTION (provided by applicant): Methylation is a ubiquitous covalent modification used to control the function of diverse biomolecules including hormones, neurotransmitters, xenobiotics, proteins, nucleic acids and lipids. More than 50 distinct methyltransferase (MTs) enzymes are present in humans, and they are being targeted for a broad range of diseases, but their involvement in neurodegenerative disease pathways is of special relevance. Modulation of neurotransmitter methylation is an emerging therapeutic strategy for the treatment of several neurodegenerative diseases, most notably Parkinsons and Alzheimers diseases, and DNA and protein MTs are also being targeted for neurodegenerative diseases and cancers of the CNS. Moreover, the involvement of some MT family members in disease pathways is intertwined with their role in metabolizing commonly prescribed drugs. The development of highly selective MT modulators is clearly a compelling medical priority. However, efforts to achieve this ...
An expert panel convened by the NIH found little evidence that Alzheimers, Parkinsons, and similar neurodegenerative diseases can be transmitted in a prion-like fashion, such as after contact with biological specimens or contaminated surgical instruments. Still, writing in the October Journal of Neuropathology and Experimental Neurology, the panel, led by Matthew Frosch, Massachusetts General Hospital, Boston, consider current research on this topic inadequate and recommend that critical questions be studied so any risk of iatrogenic spread can be truly assessed. The panel broadly agrees with a whitepaper a European working group recently published on the topic (Sep 2020 news). Toxic forms of amyloid-β, tau, and α-synuclein can act as seeds to coax misfolding and aggregation of normal versions of these proteins in healthy brains. For example, injecting minuscule amounts of toxic Aβ into mouse brain prompts rampant formation of amyloid plaques months later (Oct 2011 news). Researchers have ...
Neurodegenerative diseases are characterized by the loss of nerve cells. It is generally accepted that once the cells of the brain and spinal cord are damaged they are not easily regenerated. The three most common neurodegenerative diseases are Alzheimers disease, Parkinsons disease and Multiple Sclerosis.
A new firm, Yumanity therapeutics, has been launched with the goal of working on neurodegenerative diseases. Presently almost 50 million people worldwide suffer from multiple types of neurodegenerative disease. News on
Abstract Neurodegenerative diseases are a heterogeneous, mostly age-associated group of disorders characterized by progressive neuronal loss, the most prevalent being Alzheimer disease. It is anticipated that, with continuously increasing life expectancy, these diseases will pose a serious social and health problem in the near feature. Meanwhile, however, their etiology remains largely obscure even though all possible novel clues are being thoroughly examined. In this regard, a concept has been proposed that p53, as a transcription factor controlling many vital cellular pathways including apoptosis, may contribute to neuronal death common to all neurodegenerative disorders. In this work, we review the research devoted to the possible role of p53 in the pathogenesis of these diseases. We not only describe aberrant changes in p53 level/activity observed in CNS regions affected by particular diseases but, most importantly, put special attention to the complicated reciprocal regulatory ties existing ...
TY - JOUR. T1 - Cytokine/neurotrophin interaction in the aged central nervous system. AU - Macdonald, Nancy J.. AU - Decorti, Francesco. AU - Pappas, Todd C.. AU - Taglialatela, Giulio. PY - 2000. Y1 - 2000. N2 - Age-associated neurodegenerative diseases such as Alzheimers disease are characterised by neuronal impairment that leads to cognitive deficits. As certain affected neurons depend on trophic factors such as neurotrophins (NTs), impairment in NT function has been suggested to be a component of neuronal damage associated with such disorders. Age-related neurodegenerative diseases are also characterised by high levels of proinflammatory cytokines such as tumour necrosis factor alpha (TNFα) in the CNS. Because TNFα receptors and certain NT receptors share a high degree of homology and are capable of activating similar signalling pathways, one possibility is that altered cytokine levels may affect NT function in the aged or diseased CNS. Here we wish briefly to review the evidence ...
SingHealth Foundation Grant. Overview. Our laboratorys interests lie in identification and verification of novel key molecular targets, signaling pathways or neuro-protective agents relevant to pathogenesis and therapy of debilitating human neurodegenerative diseases, including Alzheimers disease (AD), Parkinson disease (PD) and multiple sclerosis. To achieve it, cutting-edged high throughput screening works are being performed in the lab. First, the in vitro high throughput proteomics screening plus immuno-precipitation protocols as well as cellular and molecular techniques are utilized to search and identify new key molecular targets or novel signaling pathways relevant to pathogenesis and therapy in human neurodegenerative diseases. Second, in vitro high throughput chemical library screening is being performed to identify new neuro-protective agents to modulate identified new molecular targets or signaling pathways for future clinical drugs developments. Findings from in vitro ...
Neuronal cell loss contributes to the pathology of acute and chronic neurodegenerative diseases, including Alzheimers disease (AD). It remains crucial to identify molecular mechanisms sensitizing neurons to various insults and cell death. To date, the multifunctional, autophagy-related protein Beclin 1 has been shown to be both necessary and sufficient for neuronal integrity in neurodegenerative models associated with protein aggregation. Interestingly, besides its role in cellular homeostasis, Beclin 1 has also been ascribed a role in apoptosis. This makes it critical to elucidate whether Beclin 1 regulates neuronal death and survival across neurodegenerative conditions independent of protein clearance. Here, we provide experimental evidence for a direct functional link between proteolytic cleavage of Beclin 1 and apoptotic neuronal cell loss in two independent models of neurodegeneration in vivo. Proteolytic cleavage of Beclin 1 was characterized in lysates of human AD brain samples. We developed
Neurodegenerative diseases, such as Alzheimers disease (AD), Parkinsons disease (PD), amyotrophic lateral sclerosis (ALS) and Huntingtons disease (HD) are caused by the progressive loss of neuronal integrity or acute neuron injury such as stroke or trauma in the brain and spinal cord.1-3 Current therapeutic strategies for neurodegenerative diseases are mainly aimed to decrease CNS neuron damage or brain dysfunction by conferring neuroprotection and neurogenesis.4,5 Consequently, the development of effective therapeutic medicine or discovery of new biological targets with neurogenesis activities remains an urgent need in the treatment of neurodegenerative diseases. During the past decades, various kinds of receptors, ion channels and signaling pathways associated with neurogenesis activities have been identified as potential therapeutic targets for neurodegenerative diseases. Among these, the σ1 receptor has attracted wide attention.6 σ1 receptor is one of the subtype belonging to the σ ...
Many of the key findings in neurodegenerative disease are from MIND. SOD1, the most common mutation associated with ALS was identified at MIND. MIND researchers had a critical role in identifying every one of the Alzheimers genes that has been found except for ApoE. Additionally, the gene for Huntingtons disease, which has paved the way for greater understanding of the disease, was discovered at Mass General.. ...
Many neurodegenerative diseases are characterized by the conformational change of self-proteins into amyloidogenic, pathological conformers, which share structu...
Our research focuses on identifying pathophysiological consequences of widespread RNA dysregulation in neurodegeneration in order to design, develop and test novel strategies of neuroprotective therapies.. Widespread dysregulation of the RNA metabolism has been recognised as a key pathophysiological component causing at least four neurodegenerative disorders: motor neurone disease (MND), also called Amyotrophic Lateral Sclerosis (ALS), spinal muscular atrophy (SMA), Huntingtons disease (HD) and spinocerebellar ataxias (SCAs). Widespread alteration of the transcriptome has also been reported in normal ageing of the brain and many neurodegenerative disorders are late progressive adult-onset diseases. Neurodegeneration in Parkinsons disease (PD) or Alzheimers disease (AD) is also likely to exhibit and/or involve broad alteration of the RNA metabolism and of multiple biological processes.. Although some genetic causes of these often-fatal diseases are known, the multifactorial molecular ...
A team of researchers, led by scientists at the University of California, San Diego, have identified a key player in the dramatic loss of neurons in mice and fly models, a discovery that could help illuminate the role of mitochondrial dysfunction in human neurodegenerative disorders, such as Parkinsons disease.
As a model organism |i|Saccharomyces cerevisiae|/i| has greatly contributed to our understanding of many fundamental aspects of cellular biology in higher eukaryotes. More recently, engineered yeast models developed to study endogenous or heterologous proteins that lay at the root of a given disease have become powerful tools for unraveling the molecular basis of complex human diseases like neurodegeneration. Additionally, with the possibility of performing target-directed large-scale screenings, yeast models have emerged as promising first-line approaches in the discovery process of novel therapeutic opportunities against these pathologies. In this paper, several yeast models that have contributed to the uncovering of the etiology and pathogenesis of several neurodegenerative diseases are described, including the most common forms of neurodegeneration worldwide, Alzheimers, Parkinsons, and Huntingtons diseases. Moreover, the potential input of these cell systems in the development of more
During embryonic development, sensory and motor fibers interact to form nerves in the limbs. The research team led by Dr. Andrea Huber Brösamle of the Institute of Developmental Genetics of Helmholtz Zentrum München has now elucidated how this interaction functions at the molecular level: The cell surface receptor neuropilin-1 is present in both sensory and motor nerve fibers and controls their interaction in order to correctly regulate growth. We observed that motor and sensory axons were both able to guide and lead the formation of the spinal nerves of the arms and legs, said Rosa-Eva Hüttl and Heidi Söllner, lead authors of the study and doctoral students in Dr. Andrea Huber Brösamles research group. This finding surprised the authors because it had previously been assumed that the motor axons were always responsible for establishing the correct trajectories. In the same study, the researchers created a model to better elucidate structural changes in human neurodegenerative disorders ...
Peptides that act like small molecules are highly desirable as drug candidates for targeting larger proteins and peptide specific binding sites. Hybridtides are
Ayer AH, Wojta K, Ramos EM, Dokuru D, Chen JA, Karydas AM, Papatriantafyllou JD, Agiomyrgiannakis D, Kamtsadeli V, Tsinia N, Sali D, Gylys KH, Agosta F, Filippi M, Small GW, Bennett DA, Gearing M, Juncos JL, Kramer J, Lee SE, Yokoyama JS, Mendez MF, Chui H, Zarow C, Ringman JM, Kilic U, Babacan-Yildiz G, Levey A, DeCarli CS, Cotman CW, Boxer AL, Miller BL, Coppola G. Frequency of the TREM2 R47H Variant in Various Neurodegenerative Disorders.. Alzheimer disease and associated disorders, 2019 ...
Biometals in Neurodegenerative Diseases: Mechanisms and Therapeutics is an authoritative and timely resource bringing together the major findings in the field for ease of access to those working in the field or with an interest in metals and their role in brain function, disease, and as therapeutic targets. Chapters cover metals in Alzheimers Disease, Parkinsons Disease, Motor Neuron Disease, Autism and lysosomal storage disorders.. This book is written for academic researchers, clinicians and advanced graduate students studying or treating patients in neurodegeneration, neurochemistry, neurology and neurotoxicology. The scientific literature in this field is advancing rapidly, with approximately 300 publications per year adding to our knowledge of how biometals contribute to neurodegenerative diseases.. Despite this rapid increase in our understanding of biometals in brain disease, the fields of biomedicine and neuroscience have often overlooked this information. The need to bring the ...
Many questions remain about how and when CCSVI might play a role in nervous system damage and whether venous angioplasty is helpful in treating the symptoms of CCSVI. Utilizing intravascular ultrasound (IVUS,) this pilot study will provide data that will allow researchers to evaluate venous morphology pre- and post- percutaneous angioplasty and sub-classify valve morphology as related to treatment success by distinguishing vessels which are more responsive to treatment. In addition, this study will validate the safety of valvuloplasty in various neurodegenerative disorders that involve venous obstruction ...
Abnormal proteostasis due to alterations in protein turnover has been postulated to play a central role in several neurodegenerative diseases. Therefore, the development of techniques to quantify protein turnover in the brain is critical for understanding the pathogenic mechanisms of these diseases. We have developed a bolus stable isotope-labeling kinetics (SILK) technique coupled with multiple reaction monitoring mass spectrometry to measure the clearance of proteins in the mouse brain. Cohorts of mice were pulse labeled with 13 C6-leucine and the brains were isolated after pre-determined time points. The extent of label incorporation was measured over time using mass spectrometry to measure the ratio of labeled to unlabeled apolipoprotein E (apoE) and amyloid β (Aβ). The fractional clearance rate (FCR) was then calculated by analyzing the time course of disappearance for the labeled protein species. To validate the technique, apoE clearance was measured in mice that overexpress the low-density
This study is being conducted to better understand the role of inflammation in Parkinsons disease (PD) and Alzheimers disease (AD). The investigators plan to recruit 30 PD, 30 AD/Amnestic Mild Cognitive Impairment (aMCI), and 60 age matched healthy controls in this study to study the role of immune response in PD and AD.. The study involves up to two study visits involving brief questionnaires and blood draw of up to 250cc (approximately 17 tablespoons) to be collected. More ways to participate, including 1) smaller amount blood donation (up to 100cc per visit for 1-2 visits); and 2) participation via tele-visit and mobile phlebotomy visits (blood donation up to 50cc, ~5 tubes, by a certified mobile phlebotomist at home/location of choice) now available. ...
Neurodegenerative Diseases is a bimonthly, multidisciplinary journal for the publication and discussion of advances in research on all aspects of neurodegenerative diseases. The journal focuses on Alz
Parkinsons disease is a neurodegenerative disorder of unknown cause that particularly affects areas of the brain which are involved in movement control. Research studies confirm the value of motor learning in Parkinsons disease, as well as showing improvements as a result of training.. CuPiD will develop innovative rehabilitation based on new technology, the patients needs, the principles of motor learning in Parkinsons disease. CuPiD will contribute to the challenge of engaging patients with a chronic neurodegenerative disease in intensive exercise for a considerable length of time.. ...
Parkinsons disease is a neurodegenerative disorder of unknown cause that particularly affects areas of the brain which are involved in movement control. Research studies confirm the value of motor learning in Parkinsons disease, as well as showing improvements as a result of training.. CuPiD will develop innovative rehabilitation based on new technology, the patients needs, the principles of motor learning in Parkinsons disease. CuPiD will contribute to the challenge of engaging patients with a chronic neurodegenerative disease in intensive exercise for a considerable length of time.. ...
Proteins, the components of our body that execute, control and organize basically all functions in our cells, are made out of strings of amino acids, which - like an origami - are folded into specific and complex three-dimensional structures according to their desired functions. However, since folding and maintaining of such structures is highly sensitive to cellular or environmental stress, proteins can potentially misfold or form clumps (aggregates). Such undesired protein waste can be toxic for cells and may even lead to cell death. Because several human neurodegenerative diseases are known to be linked to an accumulation of abnormal protein aggregates, basic science aimed to understand how cells remove cellular garbage is elementary for designing strategies for a potential prevention or cure of such disorders. Scientists in the laboratory of Stefan Jentsch at the MPIB now successfully used bakers yeast for screening for new cellular waste disposal pathways. Kefeng Lu, a postdoctoral ...
TY - JOUR. T1 - Quantitative measurement of postural sway in mouse models of human neurodegenerative disease. AU - Hutchinson, D.. AU - Ho, V.. AU - Dodd, M.. AU - Dawson, H. N.. AU - Zumwalt, A. C.. AU - Schmitt, D.. AU - Colton, C. A.. PY - 2007/9/21. Y1 - 2007/9/21. N2 - Detection of motor dysfunction in genetic mouse models of neurodegenerative disease requires reproducible, standardized and sensitive behavioral assays. We have utilized a center of pressure (CoP) assay in mice to quantify postural sway produced by genetic mutations that affect motor control centers of the brain. As a positive control for postural instability, wild type mice were injected with harmaline, a tremorigenic agent, and the average areas of the 95% confidence ellipse, which measures 95% of the CoP trajectory values recorded in a single trial, were measured. Ellipse area significantly increased in mice treated with increasing doses of harmaline and returned to control values after recovery. We also examined postural ...
Series: Neuroscience Research Progress. BISAC: MED057000. Multiple advanced neuroimaging applications in various neurodegenerative diseases including Parkinsons disease (PD), frontotemporal dementia (FTD), vascular dementia (VaD) and autism spectrum disorder (ASD) are covered in this book. Relatively novel techniques such as integrated PET/MRI and independent component analysis (ICA)-based dual regression (DR) methods were developed to capture multi-level molecular/functional and structural/microstructural as well as high-order inter-network coordination abnormalities. For instance, both PET dopamine transporter and striatal binding ratio reductions in the caudate and putamen were found in PD, consistent with the diffusion tensor imaging (DTI) fractional anisotropy (FA) reduction and fMRI voxel-mirrored homotopic correlation (VMHC) in the substantia nigra (swallow tail sign signature of PD). Furthermore, dopamine storage and pathway labeled with the vesicular monoamine transporter tracer ...
Hexanucleotide repeat expansions of variable size in C9orf72 are the most prevalent genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Sense and antisense transcripts of the expansions are translated by repeat-associated non-AUG translation into five dipeptide repeat proteins (DPRs). Of these, the polyGR, polyPR and, to a lesser extent, polyGA DPRs are neurotoxic, with polyGA the most abundantly detected DPR in patient tissue. Trans-cellular transmission of protein aggregates has recently emerged as a major driver of toxicity in various neurodegenerative diseases. In vitro evidence suggests that the C9 DPRs can spread. However, whether this phenomenon occurs under more complex in vivo conditions remains unexplored. Here, we used the adult fly brain to investigate whether the C9 DPRs can spread in vivo upon expression in a subset of neurons. We found that only polyGA can progressively spread throughout the brain, which accumulates in the shape of aggregate-like puncta inside
Mutations in the Valosin containing protein (VCP) gene are the cause of various neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), a form of motor neuron disease, and a rare multisystem disease which affects muscle, bone and brain. VCP is involved in a lot of different functions in cells. We know that VCP is important…
Abnormal iron accumulation within the brain is associated with various neurodegenerative diseases; however, there is debate about whether milder disorders of systemic iron loading, such as haemochromatosis, affect the brain. Arguments on both sides of the debate are often based on some common assumptions that have not been rigorously tested by appropriate experimentation. Recent research from our lab has applied high-throughput molecular techniques such as microarray to models of dietary and genetic iron loading to identify subtle but important effects on molecular systems in the brain that may go undetected by other methods commonly used in the field. In this chapter, we review the existing research in animal models and human patients and discuss the strengths and limitations of the different approaches commonly used. Using our findings as an example, we argue that transcriptomic methods can provide unique insights into how systemic iron loading can affect the brain and suggest some basic ...
A link between DNA damage and the process of aging has been firmly established (1, 2). The brain in particular is a vulnerable organ that is plagued by various neurodegenerative disorders that have been related to aging, i.e. Alzheimer and Parkinson disease. The study of the early onset of age-related neurodegenerative diseases is challenging, because there are not many confident early molecular determinants that predict their development. Therefore, progeroid syndromes (showing premature aging) are often used as a model for segmental aging as they show consistent and predictive elements of the aging phenotype (e.g. cessation of growth and development, hearing loss, and severe and progressive neuron dysfunction) (1, 3). These accelerated aging syndromes have in common that they carry defects in one or multiple proteins involved in DNA damage repair mechanisms.. A well established progeroid mouse model is the excision repair cross-complementing group 1 (Ercc1)1 gene knock-out (4, 5). The ...
28 04 2020GABA or gamma-aminobutyric acid is the major inhibitory neurotransmitter in mammals brains GABA receptors are the most common single receptor found in the synapses where neurons communicate with each other There are two known types of GABA receptor: GABA-A which comprise the primary sites of sedative drug action and GABA-B which play a role in muscle tone regulation Abstract Current treatments for insomnia such as zolpidem (Ambien) and eszopiclone (Lunesta) are γ-aminobutyric acid type A (GABA A)-positive allosteric modulators that carry a number of side effects including the potential to disrupt cognition In an effort to develop better tolerated medicines we have identified dual orexin 1 and 2 receptor antagonists (DORAs) which promote sleep in Because the GABA receptor is abundant in the cortex and is very sensitive to damage it represents a reliable marker of neuronal integrity-for example in ischemic brain damage and in various neurodegenerative diseases Part of the GABA A ...
When Dr. Jeff Bradstreet unexpectedly and tragically died in the spring of 2015, many of us wondered what would happen to the research he was doing with GcMAF, Goleic, and Bravo yogurt, which he was using to help children with autism. To my great pleasure, I am pleased to report that the research has continued and treatment options have been expanded. We are now seeing even more powerful results for the treatment of autism, cancer, chronic Lyme, chronic fatigue syndrome, and various neurodegenerative diseases. Dr. Bradstreets previous research focused on the macrophage activating factors known as GcMAF and Goleic, which he used in his clinic. Dr. Bradstreet was able to help 3 out of 4 autistic children by treating them with GcMAF or Goleic. Approximately 20% to 25% of these children lost their autism diagnosis and another 50% experienced a reduction in autistic symptoms. After the European manufacturing facility for GcMAF and Goleic was raided and closed down in the first months of 2015, Dr. ...
Elevated expression of specific transposable elements (TEs) has been observed in several neurodegenerative disorders. TEs also can be active during normal neurogenesis. By mining a series of deep sequencing datasets of protein-RNA interactions and of gene expression profiles, we uncovered extensive binding of TE transcripts to TDP-43, an RNA-binding protein central to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Second, we find that association between TDP-43 and many of its TE targets is reduced in FTLD patients. Third, we discovered that a large fraction of the TEs to which TDP-43 binds become de-repressed in mouse TDP-43 disease models. We propose the hypothesis that TE mis-regulation contributes to TDP-43 related neurodegenerative diseases.. ...
Researchers will present findings at the AANS Annual Scientific meeting of their studying testing if Intralaminar thalamic deep brain stimulation (ILN-DBS) could have an effect on dementia and other neurodegenerative diseases that cause severe cognitive dysfunction.
Recent studies in neurodegenerative conditions have increasingly highlighted that the same neuropathology can trigger different clinical phenotypes or, vice-versa, that similar phenotypes can be triggered by different neuropathologies. This evidence has called for the adoption of a pathology spectrum-based approach to study neurodegenerative proteinopathies. These conditions share brain deposition of abnormal protein aggregates, leading to aberrant biochemical, metabolic, functional, and structural changes. Positron emission tomography (PET) is a well-recognized and unique tool for the in vivo assessment of brain neuropathology, and novel PET techniques are emerging for the study of specific protein species. Today, key applications of PET range from early research and clinical diagnostic tools to their use in clinical trials for both participants screening and outcome evaluation. This position article critically reviews the role of distinct PET molecular tracers for different neurodegenerative ...
Current diagnostic approaches to neurodegenerative diseases are often flawed as they are often invasive and cannot effectively diagnose early-onset dementia. Antibody-based therapeutics for neurodegenerative diseases are very promising but often lack specificity to certain biomarkers and require invasive methods of administration such as a lumbar puncture. In this study I report a novel quantum-dot (QD) conjugated bispecific-antibody (BsAb) diagnosis system designed for Alzheimers disease. This structure is easy to synthesize and displays specificity to oligomeric amyloid-beta (Aβ), which is often present before Alzheimers symptoms starts to manifest. The bispecific antibody also binds with a weak affinity to transferrin receptors - thus potentially allowing it to cross the blood-brain barrier (BBB) via receptor-mediated transcytosis and reducing the necessity for extremely- invasive means of administration such as a lumbar puncture. The CdTe/ZnS QDs conjugated to the BsAb have multimodal, ...
The EU Joint Programme - Neurodegenerative Disease Research (JPND) has announced a EUR 30 million call for neurodegenerative disease research topped-up with EUR 10 million from the Horizon 2020 framework programme for research and innovation of the European Union.. Neurodegenerative diseases such as Alzheimers and Parkinsons are a truly global challenge. Most of these diseases remain incurable and are strongly linked with aging populations. Dementias alone affect more than 7 million people in Europe and their care is estimated to cost EUR 130 billion a year. The challenge facing the world of diagnosing, treating and caring for people affected by neurodegenerative diseases is extremely daunting and no single country alone has the expertise or resources necessary to tackle all of the big questions in this area.. JPND was established in 2009 to enable participating EU Member States to work together on the challenge of age-related neurodegenerative diseases, in particular Alzheimers. In the past ...
The role of lipids in autophagy and its implication in neurodegeneration - Neurodegenerative diseases are, at present, major socio-economic burdens without effective treatments and their increasing prevalence means that these diseases will be a challenge for future generations. Neurodegenerative diseases may differ in etiology and pathology but are often caused by the accumulation of dysfunctional and aggregation-prone proteins. Autophagy, a conserved cellular mechanism, deals with cellular stress and waste product build-up and has been shown to reduce the accumulation of dysfunctional proteins in animal models of neurodegenerative diseases. Historically, progress in understanding the precise function of lipids has traditionally been far behind other biological molecules (like proteins) but emerging works demonstrate the importance of lipids in the autophagy pathway and how the disturbance of lipid metabolism is connected to neurodegeneration. Here we review how altered autophagy and the disturbance of
The role of inflammation in the progression of neurodegenerative disease remains unclear. We have shown that systemic bacterial insults accelerate disease progression in animals and in patients with Alzheimers disease. Disease exacerbation is associated with exaggerated CNS inflammatory responses to systemic inflammation mediated by microglia that become primed by the underlying neurodegeneration. The impact of systemic viral insults on existing neurodegenerative disease has not been investigated. Polyinosinic:polycytidylic acid (poly I:C) is a toll-like receptor-3 (TLR3) agonist and induces type I interferons, thus mimicking inflammatory responses to systemic viral infection. In the current study we hypothesized that systemic challenge with poly I:C, during chronic neurodegenerative disease, would amplify CNS inflammation and exacerbate disease. Using the ME7 model of prion disease and systemic challenge with poly I:C (12 mg/kg i.p.) we have shown an amplified expression of IFN-alpha and ...
A type of white blood cell that is important to the immune system may provide hope for new therapies for amyotrophic lateral sclerosis (ALS), as well as other neurodegenerative diseases, according to a study published online today in the Proceedings of the National Academy of Sciences.
According to a new study, tetrahydrocannabinolic acid (THCA), a compound found in cannabis, may be useful in treating neurodegenerative and neuroinflammatory diseases.
GENETICS AND ENVIRONMENT. Each of the major neurodegenerative disorders may be familial in nature. HD is exclusively familial; it is transmitted by autosomal dominant inheritance, and the molecular mechanism of the genetic defect has been defined. Nevertheless, environmental factors importantly influence the age of onset and rate of progression of HD symptoms. PD, AD, and ALS are mostly sporadic without clear pattern of inheritance. But for each there are well-recognized genetic forms. For example, there are both dominant (α-synuclein, LRRK2) and recessive (parkin, DJ-1, PINK1) gene mutations that may give rise to PD. In AD, mutations in the genes coding for the amyloid precursor protein (APP) and proteins known as the presenilins (involved in APP processing) lead to inherited forms of the disease. Mutations in the gene coding for copper-zinc superoxide dismutase (SOD1) account for about 2% of the cases of adult-onset ALS. There are also genetic risk factors that influence the probability of ...
A drug that boosts activity in the brains garbage disposal system can decrease levels of toxic proteins associated with Alzheimers disease and other neurodegenerative disorders and improve cognition in mice, a new study by neuroscientists at Columbia University Medical Center has found.
Herbicides have been recognized as the main environmental factor associated with human neurodegenerative disorders such as Parkinsons disease(PD). Previous studies indicated that the exposure to glyphosate, a widely used herbicide, is possibly linked to Parkinsonism, however the underlying mechanis …
If you have a question about this talk, please contact Gabriella Heller.. Toxicity of misfolded proteins and mitochondrial dysfunction are key factors that promote age-associated functional neuronal decline and neurodegenerative disease across species. Although these neurotoxic challenges have long been considered to be cell-intrinsic, evidence now supports that misfolded human disease proteins originating in one neuron can be transferred to neighboring cells, a phenomenon proposed to promote pathology spread. Likewise, mitochondria can be sent out of the cell that made them for transcellular degradation by neighbors. We discovered and are characterizing a dramatic, but previously unknown, capacity of C. elegans adult neurons to extrude large (~5µM) vesicles that can include aggregated proteins (including human neurodegenerative disease proteins) and damaged mitochondria. Strikingly, extruded exopher contents can be found in both neighboring and remote cells. We suggest that throwing out the ...
Abstract: OBJECTIVE: While the causes of neuronal death in Parkinsons disease (PD) and other neurodegenerative disorders are still unknown, several mechanisms are under discussion: programmed vs. passive cell death (apoptosis vs. necrosis), mainly based on conflicting results on the rare presence or absence of DNA fragmentation in substantia nigra neurons using the in situ DNA-labeling (TUNEL) method. DESIGN/METHODS: In 4 cases of Parkinsons disease (PD), 2 cases of Dementia with Lewy bodies (DLB) and 3 age-matched controls, the TUNEL/ISEL method was used to detect DNA fragmentation in substantia nigra locus coeruleus and cerebral cortex [method by Gold et al. (1994)]. In addition, immunohistochemistry was performed for an array of apoptosis-related proteins, i.e. the recently described apoptosis specific protein cJun/AP1 (ASP), the proto-oncogenes c-Jun, c-Jun AP1, Bcl2, Bax, Bcl-x, p53, CD 95 (Fas/Apo-1), activated caspase 3, several heat shock proteins (alpha-B crystallin, ubiquitin), and ...
Significant progress has been made over the past two decades on the pathogenesis of individual neurodegenerative diseases, including Alzheimers disease (AD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, different neurodegenerative syndromes have been mainly studied mechanistically in isolation. There has been a lack of concerted effort to ascertain whether and how these pathogenic processes may be linked to one another. In the most recent issue of journal Acta Neuropathologica, Dr. Mingkuan Sun, William Bell and Katherine LaClair, co-first authored a report about cryptic exon incorporation in Alzheimers disease cases exhibiting TDP-43 pathology. This is the first evidence on how loss of TDP-43 function from neurons, a common shared feature with ALS and FTD, could contribute to pathogenesis of AD.. It has been known for years that other factors besides Aβ and tau also contribute to neurodegeneration and cognitive failure in AD. The most convincing evidence is ...
Bile acids, a structurally related group of molecules derived from cholesterol, have a long history as therapeutic agents in medicine, from treatment for primarily ocular diseases in ancient Chinese medicine to modern day use as approved drugs for certain liver diseases. Despite evidence supporting a neuroprotective role in a diverse spectrum of age-related neurodegenerative disorders, including several small pilot clinical trials, little is known about their molecular mechanisms or their physiological roles in the nervous system. We review the data reported for their use as treatments for neurodegenerative diseases and their underlying molecular basis. While data from cellular and animal models and clinical trials support potential efficacy to treat a variety of neurodegenerative disorders, the relevant bile acids, their origin, and the precise molecular mechanism(s) by which they confer neuroprotection are not known delaying translation to the clinical setting.
Jika anda yang sedang mencari informasi [beasiswa] [info] 8 PhD scholarships sponsored by the German Research Center for Neurodegenerative Diseases (DZNE), maka Beasiswa akan menyampaikan tentang [beasiswa] [info] 8 PhD scholarships sponsored by the German Research Center for Neurodegenerative Diseases (DZNE) seperti dibawah ini ...
Many neurodegenerative diseases are characterized by the early loss of select groups of cells in the brain, followed only later by more widespread degeneration. Understanding the cause of the enhanced vulnerability displayed by select cell groups may point towards the root causes of these diseases and lead to novel therapeutic targets. Professor Myriam Heimans lab studies the selective vulnerability and pathophysiology seen in two neurodegenerative diseases of the basal ganglia, Huntingtons disease and Parkinsons disease.. The easily recognizable ravages of Huntingtons disease and Parkinsons disease on normal motor control reflect the loss of either dopamine-producing cells (Parkinsons disease) or dopamine-receiving cells (Huntingtons disease) in the brain. Until fairly recently, patients afflicted with these diseases would be diagnosed mainly by these abnormal motor behaviors. However, it was not known why a patient was afflicted; no usually suspected causes existed. The last twenty ...
Central nervous system (CNS)-related disorders, including brain cancer, lysosomal storage disorders, traumatic brain or spinal cord injury, chronic pain, or chronic neurodegenerative diseases, such as Alzheimers, Parkinsons disease or Amyotrophic Lateral Sclerosis, still represent a major burden for the society and demand innovative and more efficacious therapeutic approaches. Indeed, delivering therapeutics to the CNS is challenging since the blood-brain barrier (BBB) must be overcome to gain access to brain cells. Moreover, monitoring drug biodistribution or target engagement is rarely feasible if not impossible, due to the limited accessibility to tissue sampling, with the exception of the cerebrospinal fluid (CSF). However, CSF analysis is not always fully informative, especially for those conditions where the analyte is not a soluble compound released in biological fluids.Recent advances in nanomaterial science and nanoparticles (NPs) technology have provided a great breakthrough in pharmacology
Nagoya, Japan - Frontotemporal lobar degeneration (FTLD) is a type of dementia that appears earlier in life than Alzheimers disease (AD). Both FTLD and AD, along with several other neurodegenerative diseases, are marked by the appearance and clustering of the protein tau in nerve cells. However, there is much left to be explored about this…
We primarily use human neurons made from induced pluripotent stem cells as well as in vitro protein aggregation models to delineate the pathogenic mechanisms of age-related neurodegenerative diseases such as Alzheimers and Parkinsons disease. Our group is largely focused on utilizing neurons from rare lysosomal diseases to study how alterations in biomolecule degradation pathways influence the accumulation and conformation of disease-linked proteins such as alpha-synuclein, abeta, and tau. Mechanistic insights gained from studies of rare lysosomal diseases are used as a way to view and elucidate the pathological mechanisms of common neurodegenerative diseases. Another major effort of the lab is to determine how amyloid formation influences cellular self-renewal mechanisms in neurons, such as lysosomal clearance of damaged macromolecules, and the effect on the aging process ...
Alzheimers disease (AD), also known as just Alzheimers, is a chronic neurodegenerative disease that usually starts slowly and gets worse over time. It is the cause of 60% to 70% of cases of dementia. The most common early symptom is difficulty in remembering recent events (short-term memory loss).[1] As the disease advances, symptoms can include problems with language, disorientation (including easily getting lost), mood swings, loss of motivation, not managing self care, and behavioural issues. As a persons condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the average life expectancy following diagnosis is three to nine years.. The cause of Alzheimers disease is poorly understood. About 70% of the risk is believed to be genetic with many genes usually involved. Other risk factors include a history of head injuries, depression, or hypertension. The disease process is ...
Parkinsons disease is a chronic neurodegenerative disease that is characterized by the loss of dopamine-producing neurons in the substantia nigra region of the brain. There is also a simultaneous loss of norepinephrine-producing neurons in a region called the locus coeruleus. Administration of methyl phenyl tetrahydropyridine (MPTP) to laboratory animals is a common model for Parkinsons disease; however, MPTP does not cause the motor deficits seen in humans with Parkinsons disease. NIEHS-supported investigators tested mice to determine whether the loss of norepinephrine neurons was necessary for the motor deficits seen in Parkinsons disease. They used transgenic mice that totally lack norepinephrine altogether. The researchers detected no motor deficits in control mice treated with MPTP - despite an 80 percent reduction in the number of dopamine-producing cells. On the other hand, the norepinephrine-lacking mice exhibited motor deficits in most tests, along with other movement disorders, ...
Clinical trials for Alzheimers and other neurodegenerative diseases are expensive and slow, in part because they cannot find enough participants. Of the 5 million people with Alzheimers in the United States alone, many never learn about trial opportunities, and for rare dementias the pool of potential volunteers is small to begin with. Online registries that allow people to be contacted about trial opportunities in their area have sprung up to speed recruitment. Some registries educate members about the disease; others establish active patient communities (May 2011 news; Nov 2013 news). Most sites ask for minimal information at sign-up, usually name, email address, birth year, and zip code. After registering, people may choose to complete more detailed health questionnaires in order to be matched to trials. Most registries include people with or without a diagnosis. In Alzheimers, researchers are beginning to test treatments in people at pre-dementia stages. These participants are hard to ...
TY - JOUR. T1 - Neurodegenerative diseases and exposure to the environmental metals Mn, Pb, and Hg. AU - Charlet, Laurent. AU - Chapron, Yves. AU - Faller, Peter. AU - Kirsch, Regina. AU - Stone, Alan T.. AU - Baveye, Philippe C.. PY - 2012/10. Y1 - 2012/10. N2 - Metal ions appear to play an important role in several neurodegenerative (ND) diseases. Evidence suggests that metal ions bind directly to causative amyloidogenic proteins and modulate their aggregation into amyloids, considered to be a key event in the etiology of ND diseases. Apart from this well-documented binding of essential metals to amyloidogenic proteins, other, non-essential metal ions have been considered to be environmental hazards for neuronal disorders, but tight causative relations have yet to be established. The present article provides a review of the potential role of manganese, lead, and mercury as environmental risk factors in ND diseases, and covers in detail environmental availability of these metals, their uptake ...
Finding biomarkers that reflect the amount of peripheral nerve damage (peripheral neuropathies) and that the biomarker will quickly drop in value in response to to effective treatment are desired goals. The tools we need for developing biomarkers for equine neurodegenerative diseases are not available. These tools include a laboratory model for each neurodegenerative disease, putative treatments, and a money bin.. There is an alternate path leading to biomarker development and that is the horizon we are chasing. The biomarker quest project identifies natural cases of disease with neurodegeneration followed by evaluating the data from those cases. Sifting through the data is a process of eliminating the negative, selecting the positive, and interpreting the in-between. I hear a jingle in there somewhere! Generally diseases follow a typical course, or pathogenesis. Interpreting enough cases points toward the direction we should take and where to concentrate our assets. Often clues to a direction ...
The results described here support the conclusion that AT-1 is the ER membrane acetyl-CoA transporter and that its function is essential for the normal physiology of the cell. The recent identification of a missense mutation in AT-1 associated with SPG42 and the fact that AT-1 is upregulated in chronic neurodegenerative diseases such as sporadic ALS and late-onset (sporadic) AD point to a crucial role in disorders that are characterized by neuronal dysfunction and/or loss.. Although initially associated with nuclear and cytosolic proteins, covalent acetylation of the ε-amino group of lysine residues also occurs in the mitochondria (Schwer et al., 2006) and in the early secretory pathway (Costantini et al., 2007). In the secretory pathway, it appears to function as a new form of post-translational regulation of membrane proteins. We initially identified the acetylation machinery while analyzing the metabolism of BACE1 (Costantini et al., 2007). Following that initial finding, we have also shown ...
An increasing number of neurodegenerative diseases are being found to be associated with the abnormal accumulation of aggregated proteins in the brain. In Parkinsons disease, this process involves the aggregation of alpha-synuclein (α-syn) into intraneuronal inclusions. Thus, compounds that inhibit α-syn aggregation represent a promising therapeutic strategy as disease-modifying agents for neurodegeneration. The formation of α-syn amyloid aggregates can be reproduced in vitro by incubation of the recombinant protein. However, the in vitro aggregation of α-syn is exceedingly slow and highly irreproducible, therefore precluding fast high throughput anti-aggregation drug screening. Here, we present a simple and easy-to-implement in-plate method for screening large chemical libraries in the search for α-syn aggregation modulators. It allows us to monitor aggregation kinetics with high reproducibility, while being faster and requiring lower protein amounts than conventional aggregation assays. We
Pro-apoptotic signaling caused by down-modulation of KIAA0358 or expression of IG20-SV4 effectively induces spontaneous apoptosis and sensitization to TNFa-induced apoptosis in neuroblastoma cells. Methods and composition to enhance cell death in neuroblastoma are provided. Methods and compositions to reduce cell death in neurodegenerative disorders are provided.
Caution: Medical devices made by Scion NeuroStim have not received marketing authorization from the US Food & Drug Administration (FDA) for use in chronic neurodegenerative diseases such as Parkinsons Disease and are not available for sale. Neuromodulation medical devices made by Scion NeuroStim are covered by the following US patents, with other US and international patents pending ...
Environmental Factors in Neurodevelopmental and Neurodegenerative Disorders presents a state-of-the-art review of the effects of environmental contaminants on the development and degeneration of the human nervous system, brought together by world-leading experts in the field. Part One describes the adverse effects that the environment can have on neurological development, and how these effects may exhibit. Specific contaminants and their possible consequences of exposure are addressed (lead, methylmercury, alcohol), as well as specific disorders and the environmental factors associated with them, such as the effect of diet on attention deficit and hyperactivity disorders. Part Two tackles neurodegenerative disorders, specifically addressing their potential neurotoxic origins, and discussing the increasing interest in the effects that early exposure may have in later life. Environmental Factors in Neurodevelopmental and Neurodegenerative Disorders is an invaluable reference for those professionals
Destruction and death of neurons can lead to neurodegenerative diseases. One possible way to treat neurodegenerative diseases and damage of the nervous system is replacing damaged and dead neurons by cell transplantation. If new neurons can replace the lost neurons, patients may be able to regain the lost functions of memory, motor, and so on. Therefore, acquiring neurons conveniently and efficiently is vital to treat neurological diseases. In recent years, studies on reprogramming human fibroblasts into neurons have emerged one after another, and this paper summarizes all these studies. Scientists find small molecules and transcription factors playing a crucial role in reprogramming and inducing neuron production. At the same time, both the physiological microenvironment in vivo and the physical and chemical factors in vitro play an essential role in the induction of neurons. Therefore, this paper summarized and analyzed these relevant factors. In addition, due to the unique advantages of physical
The neurotransmitter glutamate has been implicated in multiple neurodegenerative studies. Researchers agree that glutamate excitotoxicity undoubtedly has a role in the pathogenesis of Alzheimer disease, the most common neurodegenerative pathology affecting the elderly population. Research suggests glutamate excitotoxicity accelerates the progression of Alzheimer disease.[12] Glutamate is also implicated in the pathogenesis of Parkinson disease. Mutations in genes encoding the parkin and DJ1 proteins are present in Parkinsons disease, which are involved in the regulation of excitatory glutamate synapses. These proteins may also protect neurons against glutamate excitotoxicity.[13][14]. Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system, is targeted in the treatment of anxiety disorder, insomnia, epilepsy, and other conditions. In particular, these drugs alter GABAergic function by targeting the GABAA and GABAB receptors.[15]. Not only does ...
Neurodegenerative diseases such as Alzheimer�s disease (AD) and Parkinson�s disease (PD) are currently considered as protein misfolding diseases. Determina...
People who suffer from REM sleep behavior disorder are at increased risk of developing Parkinsons disease and dementia as they age, a new study reports. Researchers report RBD causes a lack of dopamine in the brain, and this can contribute to the development of neurodegenerative diseases.... Read More... ...
By Eric Sauter Scientists from the Florida campus of The Scripps Research Institute have uncovered a potentially important new therapeutic target that could prevent stress-related cell death, a characteristic of neurodegenerative diseases such as Parkinsons, as well as heart attack and stroke. In the study, published recently in the journal ACS Chemical Biology, the scientists showed they could disrupt a specific interaction of a critical enzyme that would prevent cell death without harming other important enzyme functions. The enzyme in question is c-jun-N-terminal kinase (JNK), pronounced junk, which has been implicated in many processes in the bodys response to stresses, such as oxidative stress, protein misfolding, and metabolic disorder. JNK also plays an important role in nerve cell survival and has become a target for drugs to treat neurodegenerative disorders such as Parkinsons disease. In recent studies, JNK has been found to migrate to the mitochondria-the part of the cell that ...
Notification may be sought. Participants may additionally consent to banking their DNA for use in future genetic research studies into neurodegenerative diseases. The blood drawn for use in the main study will also be used for extracting the DNA that will be stored for use in future research. Alternatively, specific studies on these samples may be abandoned, but data will be kept for 5 years after publication. The biospecimens and data have been provided for genetic research, for clinical, pathologic and genetic correlations, to try and identify the molecular basis of Parkinson Syndrome and related neurodegenerative disorders. The biospecimens may be destroyed or returned to collaborating Institutions, at their request and at any time. Similarly, individuals have the rights to withdraw their participation. The specific collaborating Institution only needs to notify Dr. Farrer (or the database administrator) to remove a record/sample.. ...
It has been proved that in these neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, and Huntington's disease ... Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease ... Alzheimer's disease and Huntington's disease. PCD observed in neurodegenerative diseases may be directly pathogenic; ... Alzheimer's disease (AD) is a chronic neurodegenerative disease that results in the loss of neurons and synapses in the ...
Disease: amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Huntington's disease (HD), spinal muscular atrophy (SMA ... See the Motor Neuron Fact Sheet for details regarding other motor neuron diseases. Neurodegenerative diseases of the central ... Huntington's disease (HD), and Parkinson's disease (PD). These diseases are characterized by chronic and progressive neuronal ... Neurodegenerative diseases are a heterogeneous group of complex disorders linked by the degeneration of neurons in either the ...
Main classes of neurodegenerative diseases are Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic ... These unexpected diseases hindered estrogen to get involved in neurodegenerative disease therapy. So, when applying estrogen- ... Neurodegenerative diseases are diseases caused along the process of neurodegeneration. Neurodegeneration includes structural ... Neurodegenerative diseases can disrupt the normal human homeostasis and result in abnormal estrogen levels. For example, ...
The German Center for Neurodegenerative Diseases (German: Deutsches Zentrum für Neurodegenerative Erkrankungen, (DZNE)) is an ... The center's declared aim is to develop new preventive and therapeutic approaches for neurodegenerative diseases. To accomplish ... interdisciplinary research institution that investigates neurodegenerative disease in all its facets. It is one of six "centers ... to combat the most important and widespread diseases. The DZNE is part of the Helmholtz Association of German Research Centres ...
Examples of neurodegenerative disorders include Alzheimer's disease, Parkinson's disease, and Huntington's disease. The focus ... including neurodegenerative disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD), in rodent and non-human ... "Neurodegenerative Diseases". National Institute of Environmental Health Sciences. Retrieved 2019-02-27. (Neuroscience). ... Neurodegenerative disorders are a result of neuronal loss of function over time which lead to cell death. ...
Neurodegenerative Disease. 5 (3-4): 261-263. doi:10.1159/000113719. PMID 18322407. v t e (Articles lacking in-text citations ... Moon, G.; Manktelow, T.C. (2002). "Cognitive deficits in recently diagnosed untreated patients with Parkinson's disease". ... disease (both physical and mental), medicines and drugs. The standard battery of cognitive tests in The CDR system includes ... Alzheimer's disease, and Vascular Dementia". Neurology. 54 (8): 1616-1625. doi:10.1212/WNL.54.8.1616. PMID 10762503. S2CID ...
"Alumnus Jeffrey Kordower, Founding Director of the ASU-Banner Neurodegenerative Disease Research Center, on How He Got His ... "Neurodegenerative Disease". Biodesign Institute , ASU. Retrieved 2021-04-07. "Team". Biodesign Institute , ASU. Retrieved 2021- ... The center is pursuing new battleground tactics in the war against Alzheimer's and other neurodegenerative diseases. The center ... Dysfunctional mitochondria are associated with Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, ataxias ...
"Parkinson's Disease". National Institute on Aging. Retrieved 2020-12-12. "Neurodegenerative Diseases". National Institute of ... It is the second most prevalent neurodegenerative disease, following Alzheimer's disease. It is estimated that nearly one ... Parkinson's disease is a neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra ... Animal models of Parkinson's disease are essential in the research field and widely used to study Parkinson's disease. ...
397-. ISBN 978-3-642-02912-7. Dominguez C (18 November 2010). Neurodegenerative Diseases. Springer Science & Business Media. pp ... gastroesophageal reflux disease, and dental anxiety. It reached phase II clinical trials for all of the aforementioned ...
In neurodegenerative diseases, cells of the central nervous system stop working or die via neurodegeneration. An example of ... Alzheimer's disease (AD) Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease) Cancers Charcot-Marie-Tooth disease (CMT) ... coronary artery disease) and neoplastic diseases (e.g. cancers). Many degenerative diseases exist and some are related to aging ... "Neurodegenerative Diseases". Archived from the original on 2018-07-28. Retrieved 2018-09-17. Nopoulos, PC (2016). "Huntington ...
Guam disease, or amyotrophic lateral sclerosis-parkinsonism-dementia (ALS-PDC) is a neurodegenerative disease of uncertain ... Parkinson's disease, and Alzheimer's disease. First reports of the disease surfaced in three death certificates on Guam in 1904 ... The disease was shown to be familial but not genetic. Chamorro who grew up outside of Guam had not developed the disease, and ... Holtcamp W (March 2012). "The emerging science of BMAA: do cyanobacteria contribute to neurodegenerative disease?". Environ. ...
Neurodegenerative Diseases. 8 (5): 375-380. doi:10.1159/000324373. ISSN 1660-2862. PMC 3121545. PMID 21389683. Huang, S.; ... chronic kidney disease,HIV-1 disease,tick-borne encephalitis and Lyme,malaria,hepatitis, burns,multiple organ dysfunction ... Decreased levels are often associated with ill health and disease. A growing list of insults showing loss of pGSN includes ... Ji, Lina; Zhao, Xi; Hua, Zichun (2015-01-06). "Potential Therapeutic Implications of Gelsolin in Alzheimer's Disease". Journal ...
Kaether C, Haass C, Steiner H (2006). "Assembly, trafficking and function of gamma-secretase". Neuro-Degenerative Diseases. 3 ( ... Alzheimer's disease, Proteins, All stub articles, Human chromosome 19 gene stubs). ...
Neuro-Degenerative Diseases. 4 (5): 366-75. doi:10.1159/000105157. PMID 17622779. S2CID 9020464. Lescuyer P, Allard L, ... who have found emerging evidence that indicates a role in differentiating between different neurodegenerative diseases. To ... is decreased in brains of patients with Down syndrome and Alzheimer's disease. Journal of Neural Transmission. Supplementum. ...
Neurodegenerative Disease Management. 9 (1): 5-23. doi:10.2217/nmt-2018-0033. ISSN 1758-2024. PMID 30480471. "Onpattro ( ... "FDA approves first-of-its kind targeted RNA-based therapy to treat a rare disease" (Press release). U.S. Food and Drug ... Lipschultz B, Cortez M (10 August 2018). "Rare-Disease Treatment From Alnylam to Cost $450,000 a Year". Bloomberg. Archived ... a fatal rare disease that is estimated to affect 50,000 people worldwide. It is the first small interfering RNA-based drug ...
Neurodegenerative Disease Management. 11 (5): 411-429. doi:10.2217/nmt-2020-0066. PMID 34472379. S2CID 237389009. Murphy, AP; ... Eventually the disease can affect other muscles such as the ones located in the face. By definition, LGMDs primarily affect ... The disease commonly leads to dependence on a wheelchair within years of symptom onset, although some patients maintain ... Limb-girdle muscular dystrophy is explained in terms of gene, locus, OMIM and type as follows: For a disease entity to be ...
Shen J (2 October 2013). "Function and dysfunction of presenilin". Neuro-Degenerative Diseases. 13 (2-3): 61-3. doi:10.1159/ ... Smialowska A, Baumeister R (2006). "Presenilin function in Caenorhabditis elegans". Neuro-Degenerative Diseases. 3 (4-5): 227- ... An important part of the disease process in Alzheimer's disease is the accumulation of Amyloid beta (Aβ) protein. To form Aβ, ... Most cases of Alzheimer's disease are not hereditary. However, there is a small subset of cases that have an earlier age of ...
Neurodegenerative Disease Management. 2 (6): 561-564. doi:10.2217/nmt.12.64. Laws, Keith R; Stoet, Gijsbert; O'Connor, Daryl B ... Laws, Keith R; Irvine, Karen (December 2012). "Do women with Alzheimer's disease demonstrate greater cognitive deterioration ... "Greater cognitive deterioration in women than men with Alzheimer's disease: a meta analysis". Human Psychopharmacology: ... in patients with schizophrenia and to demonstrate worse cognitive outcomes in women suffering from Alzheimer's disease. Laws' ...
Neuro-Degenerative Diseases. 7 (1-3): 170-174. doi:10.1159/000289231. ISSN 1660-2862. PMC 2859236. PMID 20197700. Murray, ... such as Alzheimer's disease and cerebrovascular disease(s). LATE has a large impact on public health. Clinical-pathologic ... In these persons, the presence of LATE-NC is associated with a swifter disease course and with more severe clinical (memory and ... In other words, the symptoms of LATE are similar to those of Alzheimer's disease. The acronym LATE stands for Limbic- ...
2002). "Is the saitohin gene involved in neurodegenerative diseases?". Ann. Neurol. 52 (6): 829-32. doi:10.1002/ana.10384. PMID ... Neuro-Degenerative Diseases. 2 (1): 28-35. doi:10.1159/000086428. PMID 16909000. S2CID 6644618. v t e (Genes on human ... which is nested in the tau locus and confers allele-specific susceptibility to several neurodegenerative diseases, interacts ... which is nested in the tau locus and confers allele-specific susceptibility to several neurodegenerative diseases, interacts ...
... voice and language in Parkinson's disease: Changes and interventions". Neurodegenerative Disease Management. 2 (3): 279-289. ... Parkinson's disease is a chronic neurodegenerative disorder that involves the loss of dopaminergic neurons in the brain. While ... They have concluded that patients with Parkinson's disease tend to struggle with specific areas of prosody; they are less able ... The degradation of prosody in Parkinson's disease over time is independent of motor control issues, and is thus separate from ...
May 2020). "A novel neurodegenerative spectrum disorder in patients with MLKL deficiency". Cell Death & Disease. 11 (5): 303. ... Schippling S (November 2017). "MRI for multiple sclerosis diagnosis and prognosis". Neurodegenerative Disease Management. 7 (6s ... Schilder disease or diffuse myelinoclastic sclerosis: is a rare disease that presents clinically as a pseudotumoural ... As of 2019, three auto-antibodies have been found in atypical MS giving birth to separate diseases: Anti-AQP4 diseases, Anti- ...
Neuro-Degenerative Diseases. 11 (3): 129-40. doi:10.1159/000336427. PMID 22626981. S2CID 46024586. Giménez-Llort L, Ratia M, ... In animal studies it has nootropic and neuroprotective effects, and is used in research into Alzheimer's disease, and although ... "Huprine X is a novel high-affinity inhibitor of acetylcholinesterase that is of interest for treatment of Alzheimer's disease ... "Huprine X and huperzine A improve cognition and regulate some neurochemical processes related with Alzheimer's disease in ...
February 2016). "Emerging therapies in Friedreich's ataxia". Neurodegenerative Disease Management. 6 (1): 49-65. doi:10.2217/ ... The disease primarily affects the spinal cord and peripheral nerves. The spinal cord becomes thinner and nerve cells lose some ... The disease evolves differently in different people. In general, those diagnosed at a younger age or with longer GAA triplet ... As the disease progresses, some affected people lose their sight and hearing. Other complications may include scoliosis and ...
... as well as diseases such as neurodegenerative diseases, atherosclerosis, and cancer. To elaborate, LRP1 mainly contributes to ... and diseases, such as neurodegenerative diseases, atherosclerosis, and cancer. The LRP1 gene encodes a 600 kDa precursor ... Neuro-Degenerative Diseases. 11 (1): 13-21. doi:10.1159/000337231. ISSN 1660-2862. PMID 22572854. S2CID 30189180. Bachmeier, ... In support of this, LRP1 expression is reduced in endothelial cells as a result of normal aging and Alzheimer's disease in ...
Neurodegenerative Disease Management. 7 (5): 331-342. doi:10.2217/nmt-2017-0017. PMID 29043889. Burman, Joachim; Tolf, Andreas ... Fatigue has been identified as common in CIDP patients, but it is unclear how much this is due to primary (due to the disease ... The Lewis-Sumner form of this condition is considered a rare disease with only 50 cases reported up to 2004. A total of 90 ... In some case EMG/NCV can be normal). Serum test to exclude other autoimmune diseases. Lumbar puncture and serum test for anti- ...
Neurodegenerative Disease Management. 9 (1): 25-30. doi:10.2217/nmt-2018-0037. PMID 30561247. S2CID 56178847. Yu, R. Z.; ...
"List of drugs in development for neurodegenerative diseases. Update June 2007". Neuro-Degenerative Diseases. 4 (6): 443-86. doi ... It was under development by Dainippon Sumitomo Pharma for the treatment of Alzheimer's disease and made it to phase II clinical ... "Current Strategies of Therapy in Alzheimer's Disease" (PDF). The Open Neuropsychopharmacology Journal. 1: 19-23. doi:10.2174/ ...
Neuro-Degenerative Diseases. 17 (6): 242-250. doi:10.1159/000478741. PMID 28787714. S2CID 1772982. Lashuel HA, Hartley DM, ... Citron M (September 2004). "Strategies for disease modification in Alzheimer's disease". Nature Reviews. Neuroscience. 5 (9): ... "Familial Alzheimer's disease with the amyloid precursor protein position 717 mutation and sporadic Alzheimer's disease have the ... However, familial Alzheimer's disease is likely to result from altered proteolytic processing. This is evidenced by the fact ...
"List of drugs in development for neurodegenerative diseases". Neuro-Degenerative Diseases. 1 (1): 50-70. doi:10.1159/000077879 ... It was studied by Aventis for the treatment of Alzheimer's disease, but was never marketed. Piracetam "The Use of Stems in the ...
... neurodegenerative diseases and other areas of human health." As a result, Klionsky was singled out by Thomson Reuters as a ... neurodegenerative diseases, and other areas of human health. Klionsky was born in 1958 in California. Although he enjoyed ...
... a neurodegenerative disease) in adults. Zika is a member of the Flaviviridae family, which includes medically important ... HIV/AIDS HIV/AIDS is considered by many in the scientific and medical community to be the most lethal infectious disease in the ... in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes ... In January 2020, the company announced initiation of efforts to develop a vaccine against novel coronavirus disease (COVID-19) ...
MSA is one of several neurodegenerative diseases known as synucleinopathies: they have in common an abnormal accumulation of ... They are most frequently due to primary neurodegenerative disease, resulting in the loss of dopaminergic nerve terminals along ... Rare diseases, Neurodegenerative disorders, Peripheral nervous system disorders). ... "Role of Neuroimaging on Differentiation of Parkinson's Disease and Its Related Diseases". Yonago Acta Medica (Review). 61 (3): ...
... diseases, Muscular dystrophies and several rare forms of neurodegenerative diseases associated with dementia. As part of the ... Parkinson's disease and Pick's disease, Amyotrophic lateral sclerosis (ALS), Huntington's disease, Creutzfeldt-Jakob disease, ... Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases, ... "The role of the ubiquitin-proteasomal pathway in Parkinson's disease and other neurodegenerative disorders". Trends in ...
... recovered during arm regeneration as this could have applications for understanding and treating neurodegenerative diseases in ...
These fluorides in the brain may cause neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease and IQ ... These diseases can cause painful responses when associated with the acid or ammonia in SDF. Crystal, Yasmi O.; Niederman, ... Silver diamine fluoride is contraindicated in patients having silver allergy, oral ulcerations and severe gum disease. ... Nature Reviews Disease Primers. 3 (1): 17030. doi:10.1038/nrdp.2017.30. ISSN 2056-676X. PMID 28540937. Hua, Yong-Mei; Chen, Jie ...
Increased mtDNA damage is a feature of several neurodegenerative diseases. The brains of individuals with Alzheimer's disease ... Liu Z, Zhou T, Ziegler AC, Dimitrion P, Zuo L (2017). "Oxidative Stress in Neurodegenerative Diseases: From Molecular ... Neurodegenerative disease, heart failure and cancer. Though the idea is controversial, some evidence suggests a link between ... Bonda DJ, Wang X, Lee HG, Smith MA, Perry G, Zhu X (April 2014). "Neuronal failure in Alzheimer's disease: a view through the ...
She is also an adjunct professor at the Mesulam Center for Cognitive Neurology and Alzheimer's Disease at Northwestern ... they examine how the mechanisms develop over the lifespan and how they are disrupted in psychiatric and neurodegenerative ...
Since moving to Cornell, his work concentrated on Alzheimer Disease and other neurodegenerative diseases. He and his coworkers ... Blass wrote: "One of the things that happens in Alzheimer's disease and a number of other neurological diseases is a decrease ... Blass's research has concentrated on brain metabolism and metabolic diseases of the brain, particularly diseases affecting the ... These diseases affect the power plants of the cell (mitochondria) and specifically a part of the mitochondria, namely the Krebs ...
Nakamura T, Lipton SA (February 2010). "Preventing Ca2+-mediated nitrosative stress in neurodegenerative diseases: possible ... The discoverers of nitromemantine have demonstrated that the amyloid-β peptide associated with Alzheimer's disease acts as an ... Lieberman B (June 17, 2013). "Reversing the loss of brain connections in Alzheimer's disease". Beaker. Sanford-Burnham Science ... is a derivative of memantine developed in 2006 for the treatment of Alzheimer's disease. It has been shown to reduce ...
... and how neuronal sub-types may be selectively affected by different neurodegenerative diseases and neurodevelopmental disorders ... In 2004, Macklis founded the Neuroscience / Nervous System Diseases Program at the Harvard Stem Cell Institute at Harvard ... Nervous System Diseases Program at the Harvard Stem Cell Institute. Macklis received a dual S.B. in bioelectrical engineering ... as well as for therapeutic screening of pathways involved in different neurological diseases. Macklis's lab was first to show ...
In the neurodegenerative disease Alzheimer's disease, the situation is reversed, with decreased levels of dolichol and ... in relation to neurodegenerative diseases (including Alzheimer's disease) in both Russia and Australia indicate considerable ... The isoprenoid changes in Alzheimer's disease differ from those occurring during normal aging, and, therefore, this disease ...
Terry was diagnosed with Huntington's disease, an inherited neurodegenerative disease in 2003. There is no known cure. In 2011 ...
Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of ... implications for Huntington's disease neuropathology". Eur. J. Neurosci. 10 (5): 1835-45. doi:10.1046/j.1460-9568.1998.00185.x ...
The amyloid material is only found in the brain and as such the disease is not related to other forms of amyloidosis. CAA is ... Subramaniam, Rathan; Barrio, Jorge (2013-10-15). Novel Imaging Techniques in Neurodegenerative and Movement Disorders, an Issue ... Verbeek, M. M.; Waal, R. M. de; Vinters, Harry V. (2013). Cerebral Amyloid Angiopathy in Alzheimer's Disease and Related ... 2002). "Dense-core senile plaques in the Flemish variant of Alzheimer's disease are vasocentric". American Journal of Pathology ...
... neurodegenerative diseases (such as Parkinson's disease), and multiple sclerosis. Anatomical changes in the chest can also ... Aspiration pneumonia was the most common reason for the emergency admission of patients with Parkinson's Disease whose disease ... Unlike some medical problems, such as stroke, dysphagia in Parkinson's Disease degenerates with disease progression. ... Most aspiration events occur in patients with a defective swallowing mechanism, such as a neurological disease or as the result ...
... been much interest in the sigma-1 receptor and its role in age-related neurodegenerative diseases such as Alzheimer's disease. ... However, in diseases such as Alzheimer's disease, there appears to be a reduction in sigma-1 receptor expression. It has been ... the sigma-1 receptor along with other receptors could increase neuron survival and function in neurodegenerative disease. The ... the endoplasmic reticulum where they may be involved in preventing endoplasmic reticulum stress in neurodegenerative diseases. ...
... implicating the glymphatic system in neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, and ... where she is the principal investigator of the Division of Glial Disease and Therapeutics laboratory. She is also Professor of ... Parkinson's disease. The glymphatic system has also been shown to interact with the recently discovered meningeal lymphatic ... has received numerous individual prizes for her contributions to the study of neuron-glia interactions in health and disease: ...
... as aggregate in the pathologically involved tissues of Parkinson's disease and well as other neurodegenerative diseases. In ... and/or progression of the neuron injury occurring in human diseases such as Alzheimer's disease and Parkinson's disease. 15d- ... the brain has been suggested to contribute to the neuron injury observed in various rodent models of neurodegenerative diseases ... "Cyclopentenone prostaglandin-induced unfolding and aggregation of the Parkinson disease-associated UCH-L1". Proceedings of the ...
... chain and can cause a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative ... liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. Clinically, NDUFAF2 ... Mutations in NDUFAF2 have been associated with complex I deficiency and mitochondrial diseases. These disorders are a result of ... Mutations in this gene have been associated with progressive encephalopathy and Leigh disease resulting from mitochondrial ...
Dusek, P., Schneider, S. A., & Aaseth, J. (2016). Iron chelation in the treatment of neurodegenerative diseases. Journal of ... Furthermore, iron mobilization from brain appears to delay the progression of some neurodegenerative diseases, in particular ... and Aaseth has studied and discussed the role of iron chelation in the disease-modifying treatment of Parkinson's disease. ... including Parkinson's disease, Alzheimer's disease, multiple sclerosis, and autism spectrum disorder (ASD). Environmental ...
... , Bacterial diseases, Bacterium-related cutaneous conditions, Medical controversies, Neurodegenerative disorders, ... Lyme disease organizations at Curlie CDC - Lyme Disease Lyme Disease Tests - Lab Tests Online NIH - Lyme Disease NICE ... "Lyme disease rashes and look-alikes". Lyme Disease. Centers for Disease Control and Prevention. 21 December 2018. Archived from ... "Lyme Disease Data and surveillance". Lyme Disease. Centers for Disease Control and Prevention. 5 February 2019. Archived from ...
... are noted for identifying the roles of three proteins in neurodegenerative diseases: tau in Alzheimer's disease, alpha- ... "New Understanding of Disease Progression and Therapy in Neurodegenerative Tauopathies", Mayo Clinic, Rochester, MN, 21 August ... of the Center for Neurodegenerative Disease Research, Director, National Institute of Neurological Disorders and Stroke (NINDS ... "Genetics of Alzheimer's Disease (March, 2002) workshops organized by NIA and the National Institute on Neurological Diseases ...
... a fatal neurodegenerative disease that affects the motor neurons in the brain and spinal cord. He released a statement to the ... Deaths from motor neuron disease, Neurological disease deaths in California, Educators from California, Educators from Oklahoma ... He died at his home on November 26, 2018, at the age of 57, due to the disease. According to his death certificate, his body ... We ask that our sincere request for privacy be honored during this time." Hillenburg was in the early stages of the disease at ...
... are being developed to treat neurodegenerative diseases. Cyclophilin inhibition may also be a therapy for liver diseases. ... Nigro, P; Pompilio, G; Capogrossi, M C (2013). "Cyclophilin A: a key player for human disease". Cell Death and Disease. 4 (10 ... J&J targets degenerative diseases in cyclophilin inhibitor partnership. Dan Stanton. 08-Dec-2015 Naoumov, Nikolai V. (November ... permeability transition pore Overexpression of Cyclophilin A has been linked to poor response to inflammatory diseases, the ...
"DLB is the third most common of all the neurodegenerative diseases behind both Alzheimer's disease and Parkinson's disease". ... January 2022). "Lewy body disease or diseases with Lewy bodies?". NPJ Parkinson's Disease (Review). 8 (1): 3. doi:10.1038/ ... Alzheimer's disease (AD), Parkinson's disease, and Parkinson's disease dementia. The APOE gene has three common variants. One, ... Parkinson's disease or Parkinson's disease dementia. This suggests some shared genetic pathology may underlie all four diseases ...
... fatigue is an important player and can be studied when researching the causes and effects of some neurodegenerative diseases. ... Hallmarks of Alzheimer's disease (AD) are impairment of cognition, aggregation of β-amyloid peptide (Aβ), neurofibrillary ... although the degrees at which it is activated in cells has been studied as result of particular pathologies and diseases. Long- ... Synaptic fatigue is more pronounced in the APP/PS1 transgenic mouse model of Alzheimer's disease. Current Alzheimer Research, 2 ...
... diseases, Muscular dystrophies and several rare forms of neurodegenerative diseases associated with dementia. As part of the ... Parkinson's disease and Pick's disease, Amyotrophic lateral sclerosis (ALS), Huntington's disease, Creutzfeldt-Jakob disease, ... Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases, ... "The role of the ubiquitin-proteasomal pathway in Parkinson's disease and other neurodegenerative disorders". Trends in ...
  • The term neurodegenerative disease refers to the principal pathology associated with disorders such as amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease and Parkinson's disease, and it is presumed that neurodegeneration results in the clinical findings seen in patients with these diseases. (
  • These models have led to the development of targeted therapies for pathways in which astrocytes participate, and this research should ultimately influence the clinical treatment of neurodegenerative disorders. (
  • Neurodegenerative diseases are incurable and devastating neurological disorders characterized by the progressive loss of the structure and function of neurons in the central nervous system or peripheral nervous system. (
  • Because of the neurotropism of Lyme disease, speculative websites and articles and even peer-reviewed journals have purported causal associations between Lyme disease and several neurodegenerative disorders, including Alzheimer disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Parkinson disease ( 6 - 11 ). (
  • We hypothesized that, if there is a link between B. burgdorferi infection and subsequent development of Alzheimer disease, ALS, MS, or Parkinson disease, the geographic distribution of these neurodegenerative disorders should correlate with that of Lyme disease. (
  • To determine if such a correlation exists, we compared the distribution of confirmed cases of Lyme disease in the United States with the distribution of deaths due to these 4 neurodegenerative disorders. (
  • We used the Moran's I test for spatial autocorrelation to assess geographic clustering of state incidence rates of Lyme disease and of death rates for the 4 neurologic disorders by using ArcGIS 10.1 (ESRI, Redlands, CA, USA). (
  • The results are of particular interest, he noted, because many therapies are already on the market that target calcium channels for cardiovascular disorders and other diseases. (
  • "Neurodegenerative diseases constitute a heterogeneous group of disorders of the central nervous system (CNS) that are characterised by a slow and irreversible loss of neuronal functions. (
  • The underlying genetics of neurodegenerative disorders tend not to be well understood. (
  • This study links HSP to other neurodegenerative disorders and can potentially facilitate further gene discovery and mechanistic understanding of neurodegenerative diseases. (
  • In this study, researchers investigated the underlying genetics of hereditary spastic paraplegia (HSP), a human neurodegenerative disease, by sequencing the exomes of individuals with recessive neurological disorders. (
  • In this review, the miRNAs role in particular neurodegenerative disorders and their possible application in medicine was discussed. (
  • Ravi Allada, M.D., Professor of Neurobiology at Northwestern University, is interested in the molecular mechanisms underlying circadian rhythms and their links to various clinical disorders, including insomnia, depression and even neurodegenerative diseases. (
  • Patients with neurodegenerative diseases, such as Alzheimer's, Huntington's and Parkinson's diseases, often suffer from sleep and circadian disorders. (
  • Understanding the link between circadian disorders and neurodegeneration, the progressive loss of structure or function of neurons, may provide important inroads towards improving the lives of patients with neurodegenerative diseases. (
  • If his hypothesis is confirmed, the research BRF funded may lead to diagnostic tests, preventative measures and treatments aimed at any underlying circadian contribution to neurodegenerative disorders. (
  • Of the many ways to target RNA transcripts, RNA interference (RNAi) has been one of the most investigated mechanisms, opening new prospects for therapeutic progress for neurodegenerative diseases, including polyglutamine (polyQ) disorders. (
  • Finally, we will discuss current progress towards preclinical and clinical application of ASOs in neurodegenerative disorders, particularly in polyQ disorders. (
  • Sodium cyanate, a neurotoxic chemical in rodents, primates and humans, is implicated in neurodegenerative disorders in protein-deficient populations subsisting in parts of Africa on the cyanogenic plant cassava. (
  • Studies suggest that curcumin has potential therapeutic value against oxidative stress-induced neurodegenerative disorders. (
  • We identified disease-causing mutations in known genes associated with neurodevelopmental disorders including GNAO1 and CDKL5 in two of four individuals. (
  • Consequently, cancer, neurodegenerative diseases or developmental disorders may arise. (
  • Definition of neurology: a science involved in the study of the nervous systems, especially of the diseases and disorders affecting them. (
  • There is an association between dopamine levels and several psychiatric and neurological disorders, including Parkinson's disease . (
  • It has been studied in pathologies such as Alzheimer's disease, Parkinson's disease, and convulsive disorders. (
  • 2. Patients with vascular dementia will be excluded, according to the criteria of the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et 1'Enseignement en Neurosciences) (NINDS-AIREN). (
  • Preclinical and clinical strategies for the treatment of neurodegenerative, cerebrovascular, and mental disorders : [workshop, Tokyo, October 31 - November 2, 1994] / volume editor T. Shibuya. (
  • They compared prefrontal cortex in 32 postmortem human brains of prospectively followed patients with Alzheimer disease, Parkinson disease with dementia, dementia with Lewy bodies, and adults without dementia (controls). (
  • Moreover, these five proteins were able to differentiate Parkinson disease with dementia, dementia with Lewy bodies, and Alzheimer disease from controls with high sensitivity and specificity, and to reliably discriminate Alzheimer disease from Parkinson disease with dementia. (
  • The risk varies by condition, ranging from just over twice as high for dementia, up to 15 times as high for motor neurone disease, the findings show, prompting the researchers to call for strategies to cut the risks of head impact and traumatic brain injury across all sports, including in training. (
  • Traumatic brain injury is a major risk factor for neurodegenerative disease and is thought to account for 3% of all dementia cases. (
  • The risk of a dementia diagnosis was just over twice as high, while that of Parkinson's disease was three times as high, and that of motor neurone disease/amyotrophic lateral sclerosis 15 times as high. (
  • Lewy body dementia is a disease that affects the elderly. (
  • This is one of many neurodegenerative disease markers we've identified to predict the likelihood of a dementia subtype, quantifying the progression of the disease, and evaluating efficacy of new treatments," says Chris Berka, principal investigator for the project and the company's CEO. (
  • This means providing comprehensive support to former players and their families, who are currently living with dementia and other neurodegenerative diseases. (
  • The structure of this lecture will be around a brief description of dementia and current treatments that are aimed really at symptomatic treatments for Alzheimer's disease. (
  • Alzheimer's disease and dementia are associated with big numbers. (
  • Multiple neuropathologic processes may underlie dementia, including both neurodegenerative diseases and vascular disease. (
  • 2] All dementia share common molecular mechanisms responsible for disease etiology and progression, such as hypoxia and oxidative stress, neuroinflammation, mitochondrial bioenergetics, neurodegeneration, and blood-brain barrier permeability. (
  • Alzheimer disease (AD) is the most common neurodegenerative disease responsible for dementia. (
  • Dementia only appears when our brains are impaired by neurodegenerative diseases. (
  • The most known neurodegenerative diseases include Alzheimer's Disease, Frontotemporal Dementia and Amyotrophic Lateral Sclerosis. (
  • There are still no effective treatments for the neurodegenerative diseases that cause dementia, and many questions remain as to the root causes. (
  • The UK Dementia Research Institute (UK DRI) is the single biggest investment the UK has ever made in neurodegenerative diseases, thanks to £290 million from founding funders the Medical Research Council (MRC), Alzheimer's Society and Alzheimer's Research UK. (
  • Our major disease interest is on Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD) and Alzheimer's Disease (AD). (
  • "Our data show that while former footballers had higher dementia rates, they had lower rates of death due to other major diseases. (
  • Alzheimer's disease related dementias (ADRD): Includes frontotemporal dementia (FTD), Lewy body dementia (LBD), vascular cognitive impairment/dementia (VCID), and mixed etiology dementias (MEDs). (
  • Other neurodegenerative diseases, such as Parkinson's disease with dementia, are included when AD is also being studied and when common pathways are described. (
  • Mortality from presenile dementia (PSD), Alzheimer's disease (AD), Parkinson's disease (PD), and motor neuron disease (MND) was examined for 27 states in the National Occupational Mortality Surveillance (NOMS) system for the period 1982 through 1991. (
  • The term "dementia" doesn't actually refer to one, specific disease. (
  • The difference between Alzheimer's disease and other dementia Alzheimer's disease and dementia do not mean the same thing. (
  • Other types of dementia While Alzheimer's disease is the most common type of dementia, there are other types as well. (
  • Dementia with Lewy bodies Dementia with Lewy bodies - caused by abnormal 'Lewy bodies' deposits of protein called alpha-synuclein inside of the brain's nerve cells - shares many similarities with Parkinson's disease. (
  • Vascular dementia The most common type of dementia after Alzheimer's disease, vascular dementia occurs when the brain's blood supply is blocked or damaged, causing brain cells to be deprived of oxygen and die. (
  • Despite decades of research, Alzheimer's disease remains a debilitating and eventually fatal dementia with no effective treatment options. (
  • Vigil said the funds will also support development of its TREM2 agonists that will be used to potentially treat more common neurodegenerative diseases such as Alzheimer's disease. (
  • Mitochondrial dysfunction has long been demonstrated as a common prominent early pathological feature of a variety of common neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). (
  • If we can further enhance our understanding of how these oligodendrocyte precursor cells mature, then it may be possible to stimulate them to replace myelin in diseases like multiple sclerosis. (
  • BUFFALO, N.Y. - Researchers at the University at Buffalo have identified a critical step in myelination after birth that has significance for treating neurodegenerative diseases like multiple sclerosis, in which myelin is lost or damaged. (
  • According to Anastassov, AXIM has a particular interest in treating neurodegenerative diseases like multiple sclerosis (MS), Parkinson's and Alzheimer's diseases. (
  • The aetiology of primary neurodegenerative diseases, such as Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), remains largely unknown. (
  • Geographic distribution of Lyme disease compared with that for deaths due to amyotrophic lateral sclerosis (ALS), Parkinson disease, multiple sclerosis (MS), and Alzheimer disease. (
  • The advice to retire from playing was grounded in science: research has shown that repeated concussions increase the risk of memory problems, mild cognitive impairment and potentially Alzheimer's disease . (
  • They also contribute to a condition called chronic traumatic encephalopathy (CTE) - a neurogenerative disease similar to Alzheimer's disease, which produces tau protein clumps. (
  • If you look at Alzheimer's disease, which we've known about for a lot longer, we're still not there in terms of having any treatments that can slow down the progression of the damage to the brain," she says. (
  • Under normal circumstances, MOCA is a key member of the squadron charged with keeping Alzheimer's disease at bay. (
  • MOCA was initially identified as a protein that binds to presenilin, a molecule that when mutated causes familial Alzheimer's disease. (
  • Alzheimer's disease is a diagnosis that strikes fear in the hearts of most people. (
  • Alzheimer's disease is the most common cause of this condition. (
  • Patients with Alzheimer's disease have a steady decline in mental capabilities as well as memory. (
  • A study published in the Journal of Alzheimer's Disease provides new insights on this subject. (
  • A 2011 study published in the International Journal of Alzheimer's Disease suggests that the bioavailability of dietary copper is thrown off kilter as a direct result of Alzheimer's, which puts the issue of copper toxicity into a whole different perspective. (
  • Additionally, several diseases can sometimes have overlapping clinical symptoms that makes diagnosis even more challenging, including Alzheimer's disease (AD), Chronic Traumatic Encephalopathy (CTE), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and argyrophilic grain disease (AGD), which highlights the critical need for better ways to identify and distinguish during life. (
  • Researchers have examined the role dynein has in neurodegenerative diseases of the basal ganglia, dementias such as Alzheimer's disease (AD), and diseases of motor neurons that include amyotrophic lateral scherosis (ALS), spinal muscular atrophy (SMA), and spino-bulbar muscular atrophy (SBMA) 2 . (
  • Then, I'll be asking what are the best disease models in which to study Alzheimer's disease, and I'll be looking at our work using prion disease and asking whether the prion disease mimics some of the hallmarks of Alzheimer's disease. (
  • A key feature, then, of the lecture will be to ask whether or not we need to tailor the drugs, particularly targeting the muscarinic receptor for different stages of Alzheimer's disease, where we might need different levels of modulation of disease. (
  • Finally, bearing in mind the adverse responses that many treatments have for Alzheimer's disease, asking whether we can develop methods by which we can reduce adverse responses, and therefore, have chronic treatment of disease that will slow the progression of neurodegenerative disease. (
  • So, as many of you will know, the feature of Alzheimer's disease is, of course, severe neuronal loss, resulting in a terminal disease state- patients die of Alzheimer's disease in the end. (
  • Our research has already contributed to the development of a drug candidate for Alzheimer's disease (AD) that is just about to enter a phase II clinical study. (
  • 1.2 GHz NMR functional structural biology research of amyloid fibrils for the study Alzheimer's disease (AD). (
  • Many scientific findings indicate the altered expression of specific miRNA in the brains of patients affected by neurodegenerative diseases (NDs) such as Alzheimer's disease, Parkinson's disease and Huntington disease. (
  • Curcumin is associated with positive effects with respect to amelioration of cognitive decay in mouse model of Alzheimer's disease. (
  • In a recently published scientific article NovaSOL ® Curcumin has demonstrated to improve mitochondrial function in a mouse model of alzheimer's disease. (
  • Neurodegenerative diseases (NDs) are chronic conditions that result in progressive damage to the nervous system , including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic lateral sclerosis (ALS). (
  • Amsterdam, NL - Last year, the FDA gave accelerated approval of the antibody aducanumab (marketed as Aduhelm by Biogen) for the treatment of Alzheimer's disease. (
  • Oxidative stress has been considered to be the main cause in the etiology of neurodegenerative diseases, which includes Parkinson's disease (PD) and Alzheimer's disease (AD). (
  • Objective To compare the general clinical conditions and oral alterations, and also evaluate the prosthesis, in subjects diagnosed with Alzheimer's disease (AD) or Parkinson's disease (PD), attended at two geriatric centers in the city of Fortaleza - Ceará. (
  • The study suggests ways to target microglia, shown here in pink among neurons, in order to treat brain diseases such as Alzheimer's disease. (
  • Genetic research suggests that cells called microglia play a key role in brain diseases such as Alzheimer's disease. (
  • Microglia associated with Alzheimer's disease have been shown to have high osteopontin levels. (
  • This analysis revealed that risk ranged from a 5-fold increase in Alzheimer's disease, through an approximately 4 fold increase in motor neurone disease, to a 2 fold Parkinson's disease in former professional footballers compared to population controls. (
  • EMFs and Alzheimer's disease (letter). (
  • The purpose of this initiative is to increase the number of early stage physician-scientists in Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD) research and improve patient care for veterans. (
  • Aduhelm was approved as the firm's first Alzheimer's disease therapy in June 2021. (
  • What is Alzheimer's disease? (
  • Alzheimer's disease is a chronic neurodegenerative disease that destroys brain cells, causing thinking ability and memory to deteriorate over time. (
  • Alzheimer's disease is not a normal part of aging, and is irreversible. (
  • The history behind Alzheimer's disease While Alzheimer's has always been with us, attempts to understand and identify the disease and its impact didn't come about until very recently in human history. (
  • How Alzheimer's disease changes the brain Alzheimer's disease can change the brain in many different ways, On this page, read about some of the changes you may expect as the disease progresses. (
  • The stages of Alzheimer's disease Alzheimer's disease is usually described in terms of stages, indicating the severity of the symptoms. (
  • Genetic testing and Alzheimer's disease Genetic testing can sometimes help identify whether a person has a high or low chance of developing Alzheimer's disease. (
  • The most effective way to prevent Alzheimer's disease and other dementias is to minimize the risk factors and make healthy lifestyle choices that benefit both your body and brain. (
  • ProMIS Neurosciences, Inc. discovers and develops precision medicine solutions for the treatment of neurodegenerative diseases, primarily Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and multiple system atrophy (MSA) in Canada. (
  • Neurons (green) derived from a patient with Alzheimer's disease. (
  • More than 95 percent of Alzheimer's disease cases have no known origin. (
  • Now, scientists from the Salk Institute have found that neurons from people with Alzheimer's disease show deterioration and undergo a late-life stress process called senescence. (
  • The researchers also discovered that targeting the deteriorating neurons with therapeutics could be an effective strategy for preventing or treating Alzheimer's disease. (
  • Our study clearly demonstrates that these non-replicating cells are going through the deterioration process of senescence and that it is directly related to neuroinflammation and Alzheimer's disease," says co-corresponding author and Professor Rusty Gage, president of the Salk Institute and holder of the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Disease. (
  • In this study, Gage and his team took skin samples from people with Alzheimer's disease and converted those cells directly into neurons in the lab. (
  • They also explored senescence markers and gene expression of post-mortem brains from 20 people with Alzheimer's disease and matched healthy controls. (
  • The Gage team found that senescent neurons are a source of the late-life brain inflammation observed in Alzheimer's disease. (
  • Targeting senescent cells could thus be a useful approach for slowing neuroinflammation and neurodegeneration in Alzheimer's disease. (
  • More work still needs to be conducted on how senescent neurons lead to Alzheimer's disease as well as the consequences of removing these neurons from the brain. (
  • Medical condition (not Alzheimer's disease) that may be contributing to cognitive impairment in the subject (substance abuse, AIDS, syphilis, stroke or other cerebrovascular disease, head trauma, brain tumor). (
  • Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease - is a neurological disease which attacks the motor neurons causing irrevocable damage in the ability to control voluntary muscle movement of the body. (
  • Currently, it is believed many neurodegenerative diseases, such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and frontotemporal lobar degenerations share the misfolded protein transmission phenomena with the prion diseases. (
  • Using cultured cells and mice as a model organism, Anne's group have found a small molecule, named Sephin1 (a selective inhibitor of a holophosphatase) which selectively binds and inhibits PPP1R15A, a regulatory subunit of the protein phosphatase PP1, to safely prolong the benefit of a phospho-signaling pathway and prevent the motor, histological and molecular defects of two, otherwise unrelated diseases in mice, Charcot-Marie-Tooth 1B and amyotrophic lateral sclerosis. (
  • Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a progressive, fatal neurodegenerative disorder that causes the loss of motor neurons, typically resulting in paralysis, respiratory failure, and death within 3-5 years of symptom. (
  • Amyotrophic lateral sclerosis is a fatal neurodegenerative disease. (
  • Where previous studies have focused on disease progression at or after onset of rod death (after postnatal day 10), transcriptome profiling of rods at days 2-6 in this new research shows major and highly specific abnormalities in expression of genes associated with mitochondria and metabolism. (
  • This research topic will showcase the current understanding of the structure and transmission property of these filamentous molecules linking the effect of conformational strains to the disease progression. (
  • I'd like to present to you our work that we've been doing for, I would say over the last 10 or 20 years, looking at novel ways of treating the symptoms and slowing the progression of neurodegenerative disease. (
  • Can we use gene therapy to prevent or half the progression of neurodegenerative disease, and can we improve the way they are delivered? (
  • Currently, there are no neuroprotective agents available that can effectively slow the disease progression. (
  • Diapocynin also halted the disease progression in a chronic mouse model of PD. (
  • By examining the level of biomarkers, we can tell the disease stage and progression, too," Dr. Hathout said. (
  • This set of non-invasive biomarkers can be easily used as a readout to monitor disease progression and response to therapies in boys with DMD, and that is our next step in this area of DMD research," Dr. Hathout added. (
  • Jan Fröhlich, Ph.D. and Dr. Manlio Vinciguerra of the Epigenetics, Metabolism and Aging FNUSA-ICRC Research team, in collaboration with a research institute at the Medical University in Varna, published a successful review summarizing current knowledge on the effect of adipomyokines / metabotrophic factors on the development and progression of cardiometabolic (CMD) and neurodegenerative diseases. (
  • This narrative article aims to determine the use of cannabidiol for the control of Current therapy for advanced diseases is refractory neurological symptoms in patients oriented towards symptom control rather with seizure syndromes and neurode- than halting their progression. (
  • The strength of the association, however, points to a potentially modifiable risk factor for neurodegenerative disease, similar to diet and exercise," says Charlene Gamaldo, MD, a coauthor and associate professor of neurology at Johns Hopkins University School of Medicine. (
  • Comparing the transcriptomic and epigenomic landscapes of these two cell types under normal and stressed conditions might yield insight into new approaches to treat neurodegenerative diseases. (
  • There are also well-developed models of human neurodegenerative diseases in flies. (
  • The misfolded proteins aggregate to adopt a amyloid-like ordered fold and show a similar filamentous nature across different neurodegenerative diseases. (
  • The goal of this topic is to combine the cellular, molecular, and structural basis of understanding on prion -like transmissions of misfolded proteins associated with different neurodegenerative diseases. (
  • What are the common pathways affected across different neurodegenerative diseases? (
  • FDA launched the FDA Rare Neurodegenerative Disease Grant Program when the Accelerating Access to Critical Therapies for ALS was enacted. (
  • Paolo, affected by a rare neurodegenerative disease, only one of two cases in Italy, had already run up and sat by the Pope during a general audience in 2021. (
  • we see it in Alzheimer's, ALS, and Huntington's disease. (
  • Huntington's disease is a hereditary neurological disorder of the central nervous system. (
  • Huntington's disease is a fatal hereditary disease that destroys neurons in areas of the brain involved in movement, intelligence, and emotions. (
  • In recent days, Huntington's disease or HD is generally used by physicians. (
  • Our understanding of the normative biology of astrocytes has been aided by the development of animal models in which astrocyte-specific proteins and pathways have been manipulated, and mouse models of neurodegenerative diseases have also revealed astrocyte-specific pathologies that contribute to neurodegeneration. (
  • We now have a better understanding of the natural history of neuronal cell death in degenerative disease," said the study's lead investigator, Anand Swaroop, Ph.D., senior investigator and chief of the NEI Neurobiology Neurodegeneration and Repair Laboratory, part of the National Institutes of Health. (
  • The goal is to one day use this supplement to prevent or reverse the course of neurodegeneration in humans, and thus cure this disease," said Gleeson. (
  • Modulation of endogenous cellular defense mechanisms via the vitagene system represents an innovative approach to therapeutic intervention in diseases causing chronic tissue damage, such as in neurodegeneration. (
  • The process of neurodegeneration is implicated in several degenerative diseases of the retina. (
  • The group's work is focused on mechanisms of neurodegeneration and subsequent loss of vision, particularly the early diagnosis and management of age-related neurodegenerative processes. (
  • Specifically with regard to Wilson's disease, Alzheimer's and other forms of neurodegeneration and cognitive decline, copper was found to play a major role in triggering the inflammation, autoimmunity and fibrosis linked to these and other diseases. (
  • The observed neuron loss, protein aggregation, and/or axonal transport deficits are all pathophysiological hallmarks of neurodegeneration, thus motivating further examination of dynein's role(s) in various neurodegenerative diseases (Fig. 2). (
  • We don't know if AICAR will work in mice or humans yet, but our work in cells definitely points in that direction," said co-author Vincent Cantagrel, PhD. "This rare disorder might be one of the first treatable neurodegenerative diseases in humans. (
  • Parkinson's disease is a serious and fatal degenerative disorder that affects the central nervous system. (
  • Parkinson's disease (PD) is a devastating neurodegenerative disorder characterized by progressive motor debilitation, which affects several million people worldwide. (
  • Parkinson's disease (PD) is the most common neurodegenerative movement disorder, estimated to affect 1% of the population over 65 years of age. (
  • Researchers from the Karolinska Institute have utilized in-depth quantitative proteomics to explore synaptic dysfunction in neurodegenerative dementias . (
  • Several drugs in our laboratory have been delivered to rodent models of neurodegenerative disease and shown efficacy. (
  • Occupations with statistically significant increased proportionate mortality for deaths occurring between the ages of 15 and 55yr were also examined since a relatively early age at death might indicate that an occupational factor was involved in the etiology or pathogenesis of the diseases. (
  • His research interests include diagnostic imaging, 3D medical image visualization and processing, haemodynamic analysis of cardiovascular diseases and 3D printing in cardiovascular disease. (
  • This is important in the treatment of cardiovascular diseases in the aging population. (
  • In his book "History of Selenium", Richard Morrill takes a closer look at some of the studies that link improved selenium status to lower cancer rates and fewer cardiovascular diseases. (
  • Acute kidney injury (AKI) is a life-threatening disease with high mortality characterized by an abrupt decrease of the kidney glomerular filtration rate, extra-kidney consequences (cardiovascular diseases, lung injury, neurological impairment) and high risk of secondary chronic kidney disease (CKD). (
  • Sleep restriction increases the risk of developing cardiovascular diseases by augmenting proinflammatory responses through IL-17 and CRP. (
  • The authors concluded that these particular synaptic proteins are important for predicting and discriminating between neurodegenerative diseases, and should be targets for early disease intervention. (
  • Synaptic Proteins Help Distinguish Neurodegenerative Diseases - Medscape - Jan 28, 2019. (
  • The deposition of misfolded proteins is a defining feature of many age-dependent human diseases, including the increasingly prevalent neurodegenerative diseases. (
  • Therefore, improving the cells' ability to deal with misfolded proteins could be useful to reduce and prevent neurodegenerative diseases. (
  • Research led by Anne Bertolotti, in the LMB's Neurobiology Division, has identified a novel, selective and safe pharmacological approach to boost a natural cellular defense against misfolded proteins and thus safely preventing protein misfolding diseases in mice. (
  • This demonstrates that selective inhibition of PPP1R15A can safely prevent two neurodegenerative diseases caused by the misfolding of proteins in mice. (
  • Researchers from the BU CTE Center have found that immune-related proteins could help differentiate between neurodegenerative diseases and provide additional candidates for biomarkers or new therapeutic targets. (
  • They analyzed the concentration of 71 different immune related proteins and used a statistical technique to identify if specific clusters of proteins were most correlated with a specific disease. (
  • After determining a cluster of proteins for each disease, they took the top five proteins for each cluster to determine which protein was the strongest possible biomarker candidate. (
  • A common feature of many neurodegenerative diseases is the presence of aggregates of misfolded proteins (intracellular inclusions) in regions of the CNS that can serve as neuropathological hallmarks for disease diagnosis 1 , 2 . (
  • A ''perfect storm'' of genetic mutations, toxic proteins and a defect in natural cell recycling has been uncovered in Queensland Brain Institute research that could lead to treatments for neurodegenerative diseases such as Alzheimer's and Parkinson's. (
  • The presence of toxic and disease-associated proteins, including tau, in the cells can also increase mutation levels, because they can block the activity of PDR-1. (
  • The discoveries suggest that two hallmarks of virtually all neurodegenerative disease - mitochondrial dysfunction and the effects of toxic or disease-associated proteins - converge at the mitochondrial DNA. (
  • Various oxidative events implicated in many diseases is due to oxidative stress which include alteration in mitochondrial proteins, mitochondrial lipids and mitochondrial DNA, which in turn leads to damage nerve cells as they are metabolically very active. (
  • At the cellular level, which proteins in the human body are affected by neurodegenerative disease - what are the causes and consequences? (
  • The company's proprietary discovery platform comprises ProMIS and Collective Coordinates algorithms to predict novel targets known as disease specific epitopes on the molecular surface of misfolded proteins. (
  • The findings, published in Human Molecular Genetics, could point to new therapeutic targets for retinal degenerative diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). (
  • Hormetic mechanisms are reviewed as possibility of targeted therapeutic manipulation in a cell-, tissue- and/or pathway-specific manner at appropriate points in the neurodegenerative disease process. (
  • They also raise the possibility that detrimental myokines resulting from inactivity and muscle disease states could become a novel focus for therapeutic intervention. (
  • Additionally, they suggest that better understanding of the neuroinflammatory signature that is specific to individual neurodegenerative diseases may lead to identifying more specific biomarkers for all diseases and ultimately discover novel therapeutic compounds. (
  • Further studies on aging and telomeres may provide valuable insights for developing therapeutic strategies for age-related diseases . (
  • The results suggest potential therapeutic targets for Alzheimer's and other diseases involving microglia. (
  • A major focus of our research is the discovery of therapeutic strategies for various human diseases based on our fundamental molecular and cellular biology research. (
  • Several neurodegenerative diseases are caused by single gene mutations that lead to protein dysfunction and subsequent pathological cascade. (
  • Scientists have known for some time now that exposure to blue-green algae is linked to increased incidence of several neurodegenerative diseases. (
  • Biogen has several drug candidates in phase 3 trials in neurology and neurodegenerative diseases and has launched Spinraza with partner Ionis. (
  • Application of the international classification of diseases to neurology : ICD-NA. (
  • BILLERICA, Massachusetts - March 29, 2021 - At the Experimental Nuclear Magnetic Resonance Conference 2021 ( ENC ), Bruker Corporation (Nasdaq: BRKR) announces that the Forschungszentrum Juelich (FZJ), Germany has expanded its research into functional structural biology in neurodegenerative diseases with the addition of a 1.2 GHz Avance ™ nuclear magnetic resonance (NMR) spectrometer. (
  • One of the hallmarks of Parkinson's disease is amyloid formation of a particular human protein, called alpha-synuclein. (
  • And in this study the researchers wanted to find out if the risk of neurodegenerative disease might also be higher among former rugby players than it is among the general population. (
  • But researchers are working on ways to be able to clinically determine if someone has the disease in the same way we do for Alzheimer's. (
  • Researchers at the University of California, San Diego School of Medicine and Rady Children's Hospital-San Diego have identified the gene mutation responsible for a particularly severe form of pontocerebellar hypoplasia, a currently incurable neurodegenerative disease affecting children. (
  • The researchers tested their AICAR-based treatment in genetic models of the disease and in human cells. (
  • Researchers have critically evaluated these proposed biologic associations between Lyme disease and Alzheimer disease, ALS, MS, and Parkinson disease, but none have found evidence of an association ( 12 - 21 ). (
  • Researchers from the University of Michigan in Ann Arbor uncovered data that suggests having too much free copper in the blood may be involved in actual disease pathogenesis, meaning free copper may be one of the primary pathways through which disease emerges and takes hold. (
  • Researchers will develop and validate a new MRI imaging technique to visualize how neural degeneration actually occurs over time in a single neural circuit in Parkinson's disease. (
  • According to the researchers, these results highlight how important the immune system is to neurodegenerative diseases. (
  • Pretty but deadly: researchers now understand how blue-green algae is linked to neurodegenerative diseases. (
  • Summary: Increasing fish consumption could help to lower the risk of developing Parkinson's and other neurodegenerative diseases, researchers report. (
  • Children's National Health System researchers and other teams have uncovered a wide range of blood biomarkers in patients with Duchenne Muscular Dystrophy (DMD) that may provide significant insights into evaluating stages of the rare and deadly disease, and create the opportunity for future drug development to combat it. (
  • The researchers found highly significant changes in the concentration levels of 44 biomarkers that reflected various stages of the disease, Dr. Hathout said. (
  • The prospect of cell therapy for incurable neurodegenerative disease excites scientists, the public, and patients alike. (
  • He ended up with a single, step-by-step process for axon degeneration that for the first time linked together a number of diseases and conditions, including a form of mental retardation in humans. (
  • Because imaging of the glymphatic system in humans is not yet possible, additional research is needed to establish whether the relationship between neurodegenerative disease and supine sleep is causal. (
  • Mutations in dynein (or dynactin) underlie some neurodegenerative diseases in humans, manifested by axonal transport defects, neuron degeneration, locomotor abnormalities, and/or other neural deficits 4-8 (Figs. 1A, 1B). (
  • Selenium deficiency diseases are known in both animals and humans. (
  • COVID-19 is a respiratory disease caused by a new coronavirus not previously identified in humans. (
  • FDA is developing future grant and contract opportunities to develop tools, methods and processes to characterize the natural history of rare neurodegenerative diseases, identify molecular targets for these diseases and to increase efficiency and productivity of clinical development of therapies. (
  • It has been shown that WS[60]FDs influence the therapeutically important targets of the Alzheimer disease by inhibiting the catalytic activity of the monoaminooxidase B in vitro , decreasing the level of free radical species and behaving as positive modulators of AMPA receptors of Purkinje neurons in the cerebellum of rats. (
  • Learning more about how microbes and neurons communicate with one another may reveal new molecular targets for developing better treatments for neurological diseases. (
  • Additionally, they may provide novel insights into neurodegenerative pathophysiology and suggest unanticipated candidate targets for therapy. (
  • Vigil Neuroscience, which is focused on developing treatments for neurodegenerative diseases, raised $90 million in a Series B . The funds will be used to advance its pipeline of microglia-targeted medicines. (
  • In its 21 years of operation, Jacob's Ladder raised more than $3 million for research, education and awareness of neurodegenerative illnesses, as well as research into treatments. (
  • These cannabinoid treatments can also be useful against eczema and other diseases which are not neurodegenerative themselves but involve neurological processes. (
  • We believe that this will ultimately lead to treatments against devastating mitochondrial diseases and a range of neurodegenerative diseases. (
  • Dr. Chen was able to do this, thereby connecting the disease pathology with the molecular biology," says Schubert. (
  • These are to be achieved using novel non-invasive techniques to assess structural and functional changes in different models of disease and their treatment, with a view to offering quick and effective translation to the clinical arena. (
  • Prion diseases are characterized by the transmission of infectious protein species that can cause clinical symptoms. (
  • Sponsors of human gene therapy (GT) products for neurodegenerative diseases affecting adults and children should initiate first-in-human clinical trials in adults before undertaking pediatric trials, according to new draft guidance the FDA released last week. (
  • Although distinct in the areas of the nervous system affected, these diseases do share common clinical pathological features. (
  • Led by consultant neuropathologist Dr Willie Stewart, honorary clinical associate Professor at the University of Glasgow, the FIELD study found that former professional footballers had an approximately three and a half times higher rate of death due to neurodegenerative disease than expected. (
  • Clinical features overlap with many neurodegenerative syndromes and specifically Huntington disease. (
  • This is novel since it provides more possible biomarkers to help better identify diseases like CTE, AD, PSP, CBD or AGD during life. (
  • Richard Perrin's laboratory studies the proteomes of cerebrospinal fluid and blood to identify new biomarkers for early diagnosis, prognosis, staging and monitoring of neurodegenerative diseases. (
  • There is no evidence that Parkinson's disease is related to the genetic makeup of an individual. (
  • Then they will use this MRI imaging technique to validate its potential for monitoring experimental gene therapies in Parkinson's disease patients. (
  • MRI imaging currently is not equipped to visualize neural circuits in the "nigro-striatal tract," which degenerates in Parkinson's disease, because the tract is located so deep in the brain. (
  • In Parkinson's disease, the dopamine-producing cells die, and the cells that control movement degenerate. (
  • These viruses will serve as a vehicle for delivering four types of biological "contrast agents" that they hypothesize will enhance the ability of MRI imaging to show the neural circuits involved in Parkinson's disease. (
  • Then they will use green fluorescent protein with this technique to label and monitor genes that potentially be gene therapies for Parkinson's disease. (
  • Once the imaging technique itself is validated, this MRI imaging technology can be directly applied to assessing gene therapy in Parkinson's disease patients. (
  • Once this MRI imaging technique is validated in the Parkinson's animal model, it will provide an entirely new way to assess experimental gene therapies in Parkinson's disease patients. (
  • A growing body of research shows that exercise can enhance brain function and delay, or even prevent, the onset of neurodegenerative diseases such as Alzheimer's and Parkinson's disease . (
  • We found evidence that defects in PINK-1 and PDR-1, which can cause early-onset Parkinson's disease, can drive these mutations to higher levels in brain cells,'' Dr Zuryn said. (
  • Amsterdam - The Journal of Parkinson's Disease and its publisher IOS Press are proud to announce the two articles that have won the 2022 Parkinson Prize. (
  • Amsterdam, NL - In this special supplement to the Journal of Parkinson's Disease , "The Immune System in Parkinson's Disease," experts highlight the latest. (
  • Parvalbumin, a protein found in great quantities in several different fish species, has been shown to help prevent the formation of certain protein structures closely associated with Parkinson's disease. (
  • Parkinson's disease can adversely affect the quality-of-life. (
  • We conducted a systematic review and meta-analysis of global literature on the quality-of-life of patients with Parkinson's disease and examined the association between patient characteristics and quality-of-life. (
  • We included articles published in English that used the Parkinson's disease questionnaire to estimate the quality-of-life score and to identify the determinants of quality-of-life in patients with Parkinson's disease. (
  • In total, 41 studies with data from 4060 patients who had Parkinson's disease met our inclusion criteria. (
  • 0.001), indicating the lowest quality-of-life of patients with Parkinson's disease. (
  • Although the global score in patients with Parkinson's disease indicated an acceptable quality-of-life, there is a possibility for improvements. (
  • The findings of this study can inform evidence-based strategies by health policymakers and clinicians to enhance the quality-of-life of patients with Parkinson's disease. (
  • WHO defines health-related QOL as "an individual's of Parkinson's disease is still unknown, but genetic perception of the impact of health and disease on the factors (in 10 - 15% of all patients with the disease) and physical, mental and social aspects of life" (12) . (
  • Figure 2: Potential astrocyte dysfunction in neurodegenerative diseases. (
  • Sawhney Shalini K.. Oxidative stress, Mitochondrial dysfunction and Neuro-degenerative diseases: A Review. (
  • Recent research on the dysfunction and function of PD associated genes has provided new fundamental insights into biochemical pathways that are linked with the disease process This review includes source of free radical generation, mitochondrial dysfunction and the mechanism involved in neurodegenerative diseases which involves both PD as well as in AD. (
  • Existe limitada información respecto al uso de search of information in cannabidiol en enfermedades neurodegenerativas, por lo que no se ha evidenciado su efectividad. (
  • In that way, we can target different pathways into the disease, monitor responses to therapy, and target a drug for the condition. (
  • Additionally, it helps us better understand the mechanisms behind each disease," says corresponding author Jonathan Cherry, Ph.D., a research health scientist at the VA Boston Healthcare System and assistant professor of pathology and laboratory medicine at Boston University Chobanian & Avedisian School of Medicine. (
  • The animal model used in the study also will allow scientists to better understand the processes behind the formation of the protein aggregates that are common to most neurodegenerative diseases. (
  • MOCA is only found in neurons and regulates the expression of the beta amyloid protein responsible for the Alzheimer's plaques that are the hallmark of the disease. (
  • Protein aggregates are common features of most age-related neurological diseases," says Chen, the first author of the study. (
  • Pick's disease will cause a slow shrinking of the brain cells due to an excessive build-up of protein. (
  • However, recent advances in structural biology have led to an increase in structural information about these filaments, showing differences in their packing at high resolution in different disease types, suggesting a link between the structure and biological function of protein aggregates in different disease forms. (
  • However, an important caveat is that it's likely there won't be a single 'magic protein ' for any disease diagnosis. (
  • Sodium cyanate alters glutathione homeostasis in rodent brain: relationship to neurodegenerative diseases in protein-deficient malnourished populations in Africa. (
  • This loss in protein homeostasis is associated with several age-related diseases. (
  • The agency awards grants and contracts to public and private entities to cover costs of research and development of interventions intended to prevent, diagnose, mitigate, treat or cure ALS and other rare neurodegenerative diseases in adults and children. (
  • Funding for this research came, in part, from the National Institutes of Health (grants HD070494, NS048453), the Howard Hughes Medical Institute, California Institute for Regenerative Medicine, UCSD Christini Fund, Jane Botsford Johnson Foundation, Broad Institute, Center for Inherited Disease Research and Simons Foundation Autism Research Initiative. (
  • The EU Joint Programme - Neurodegenerative Disease Research (JPND) is the largest global research initiative aimed at tackling the challenge of neurodegenerative diseases, in particular, Alzheimer's. (
  • Age-adjusted death rates of Alzheimer disease, ALS, MS, and Parkinson disease during the same time period were obtained from the CDC WONDER (Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research) database ( ). (
  • A special issue of the journal Brain Plasticity explores research on how exercise-induced activation of peripheral systems may improve cognitive function and delay or prevent the onset of neurodegenerative diseases. (
  • This research could be a first step towards developing drugs to prevent neurodegenerative diseases. (
  • Professor Dieter Willbold, Director of the Institute of Physical Biology at Heinrich Heine University (HHU) in Duesseldorf, Germany, and Director of the IBI-7 at FZJ explained: "The new 1.2 GHz system will be an important component of the Juelich Center for Structural Biology (JuStruct) , contributing to translational research in aging and age-related neurodegenerative diseases. (
  • Dr. Matthias Stoldt, manager of the Biomolecular NMR center, jointly run by FZJ and HHU, is pleased with the progress: 'Even now, shortly after the acceptance of the 1.2 GHz NMR, we have obtained initial spectra of valuable disease research samples. (
  • Our research looks at the similarities and differences between these diseases to find the keys to slow or halt loss of brain cells at the earliest stages. (
  • Research in the Josef Coresh Lab focuses on cardiovascular epidemiology, kidney disease and gen ... etic epidemiology. (
  • Los efectos del cannabidiol lo convierten en una alternativa, of the title and research adicional a la terapéutica convencional, para el control de síntomas en trastornos neurológicos, disminuyendo de forma objectives, exhaustive sostenida el número total de episodios con un perfil de seguridad aceptable. (
  • Intranasal (i.n.) administration is a relatively novel technique to target therapeutics to the central nervous system for the treatment of neurodegenerative and other brain diseases. (
  • ASOs are emerging as a class of therapeutics with high potential to treat diseases affecting the CNS. (
  • U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Division of Surveillance, Hazard Evaluation and Field Studies, Surveillance Branch. (
  • Centers for Disease Control and Prevention. (
  • The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. (
  • The Centers for Disease Control and Prevention (CDC) cannot attest to the accuracy of a non-federal website. (
  • According to the Centers for Disease Control and Prevention (CDC) , 6.1 million children living in the United States in 2016 had received a diagnosis of ADHD . (
  • Reports of confirmed Lyme disease cases submitted to the National Notifiable Diseases Surveillance System during 2001-2010 ( 2 ) were used to calculate state-specific, age-adjusted incidence rates of Lyme disease. (
  • The company believes this platform will harness the cellular chaperome network, potentially improving drug safety and efficacy due to selective targeting of disease tissues. (
  • We are finding potentially new non-invasive tools to monitor DMD patients and reduce the burden during visits to the clinic," said Dr. Hathout, "and we hope, other rare and debilitating neuromuscular and neurodegenerative diseases. (
  • Keshan disease is a potentially fatal heart muscle disease that was first diagnosed in selenium-poor regions of China. (
  • The company is developing an advanced epigenetic drug called apabetalone for the treatment of patients with cardiovascular disease, diabetes mellitus, chronic kidney disease, peripheral artery disease, orphan diseases, and neurodegenerative diseases. (
  • At School of Bioscience we aim to study many important diseases including, but not limited to, cancer, autoimmune diseases, neurodegenerative diseases, heart and respiratory diseases, diabetes and tuberculosis. (
  • This is especially important in the case of elderly patients with other diseases such as hypertension and/or diabetes, or those who are immunosuppressed. (
  • Risk varies by condition: up to 15 times as high for motor neurone disease. (
  • Many neurodegenerative diseases are caused by defects in this kind of quality control," he said. (
  • The limited regenerative capacity of the heart is a major factor in morbidity and mortality rates: Heart malformation is the most frequent form of human birth defects, and cardiovascular disease is the leading cause of death worldwide. (
  • however, an inverse correlation was detected between Lyme disease and Alzheimer disease. (
  • The absence of a positive correlation between the geographic distribution of Lyme disease and the distribution of deaths due to Alzheimer disease, ALS, MS, and Parkinson disease provides further evidence that Lyme disease is not associated with the development of these neurodegenerative conditions. (
  • We compared Lyme disease incidence rates in each state with death rates for Alzheimer disease, ALS, MS, and Parkinson disease. (
  • These patients have what is described in medical textbooks as an untreatable disease, yet show mutations in a neuronal pathway that should be amenable to medication," said study co-author Naiara Akizu, PhD, a member of Gleeson's lab. (
  • Therefore, our long term goal is to understand how extracellular signals and transcription factors control cell fate and apply that knowledge to differentiate ESC into disease relevant neuronal cell types. (
  • These studies demonstrate that i.n. administration also has potential for the treatment of Huntington disease (HD). (
  • Emerging information about Chlamydia pneumoniae in disease & its treatment. (
  • There is no effective treatment for DMD and the disease cannot be cured. (
  • How does disease affect the functions of brain cells such as the communication between neurons or the structural integrity of the neurons? (
  • Therefore, successful in vitro differentiation protocols to be applied either for cell based therapies or disease modeling should produce neurons with defined generic and subtype identity. (
  • As with many neurodegenerative diseases, both rare autosomal-dominant forms of AD and more common sporadic forms with genetic risk factors without causative mutations exist. (
  • Since December 2019, more than 60 million people have been diagnosed with coronavirus disease 2019 (COVID-19) worldwide, while. (
  • 2019). Elevated concentrations of NfL have also been associated with disease severity in these patient populations, including in MS and other neurologic conditions (Disanto et al. (
  • The disease was first detected in China in 2019 and has spread to the rest of the world. (
  • User may consult crosswalks for ICD10 and 2000 Census industry category codes ( Chronic Disease and Industry Categories ). (
  • however, a variable but measurable amount of AD pathologic changes exist in most cognitively intact elderly individuals who undergo autopsy, indicating that AD is a chronic disease with latent and prodromal stages and suggesting that individuals may have varying abilities to compensate, either biologically or functionally, for the presence of AD. (
  • Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex chronic disease, rooted in multi-system dysfunctions characterized by unexplained debilitating fatigue. (
  • There are no approved therapies for this disease. (
  • Therapies could target these genes to treat disease by shifting microglia from a pathogenic state to a healthy state. (
  • Embryonic stem cell (ESC) differentiation has the potential to be instrumental in cell based therapies and in vitro disease modeling and chemical screens. (
  • As part of the alternative therapies for the control of refractory symptoms in advanced diseases, the use of cannabidiol stands out. (
  • Their findings, reported in the current issue of the Journal of Neuroscience , show how neurodegenerative disease starts, initiating in the nerve ending and inducing gradual changes, like a chain reaction over a long time. (
  • These findings give insight into how genetic variations might contribute to Alzheimer's and other diseases of the brain. (
  • Rod Petrie, Scottish FA President: "We welcome the findings of this important study - the most comprehensive one ever commissioned into neurodegenerative disease in former professional footballers anywhere in the world. (

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