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Neurodegenerative DiseasesNerve DegenerationAmyotrophic Lateral SclerosisNeuronsAlzheimer Diseasetau ProteinsHuntington DiseaseBrainParkinson Diseasealpha-SynucleinNerve Tissue ProteinsTauopathiesNeuroprotective AgentsDisease Models, AnimalInclusion BodiesHeredodegenerative Disorders, Nervous SystemProteostasis DeficienciesMicrogliaPrionsPrion DiseasesMice, TransgenicSynucleinsAmyloid beta-PeptidesSpinocerebellar AtaxiasFrontotemporal Lobar DegenerationCell DeathOxidative StressMutationTrinucleotide Repeat ExpansionFrontotemporal DementiaFriedreich AtaxiaMitochondriaAutophagyNeuronal Ceroid-LipofuscinosesGuamAmyloidAgingDementiaProtein FoldingCells, CulturedNeurofibrillary TanglesLewy Body DiseaseAstrocytesPeptidesNeurotoxinsParkinsonian DisordersSuperoxide DismutaseMice, Inbred C57BLModels, BiologicalLewy BodiesAxonal TransportCentral Nervous SystemTrinucleotide RepeatsMotor Neuron DiseaseSupranuclear Palsy, ProgressiveMitochondrial DiseasesMotor NeuronsUbiquitinCentral Nervous System DiseasesHippocampusCycasIron-Binding ProteinsProteasome Endopeptidase ComplexMuscular Atrophy, SpinalCerebral CortexPick Disease of the BrainSignal TransductionCell SurvivalRNA-Binding Protein FUSNeurogliaGliosisApoptosisGene Expression RegulationNervous System DiseasesPlaque, AmyloidReactive Oxygen SpeciesMultiple System AtrophyNuclear ProteinsAnimals, Genetically ModifiedSubstantia NigraMolecular ChaperonesPrPSc ProteinsImmunohistochemistrybeta-SynucleinRotarod Performance TestAmino Acids, DiaminoParkinson Disease, SecondaryAxonsIntranuclear Inclusion BodiesDNA Repeat ExpansionSpinal CordDopaminergic NeuronsAtrophyBlotting, WesternCorpus StriatumTDP-43 ProteinopathiesAntioxidantsCyclin-Dependent Kinase 5PhenotypeNeurofilament ProteinsAmyloid beta-Protein PrecursorNeuroaxonal DystrophiesAtaxiaCell LineEncephalitisPrPC ProteinsTrauma, Nervous SystemCreutzfeldt-Jakob SyndromeCerebellumMolecular Sequence DataMice, KnockoutGlial Fibrillary Acidic ProteinMachado-Joseph DiseaseLysosomesNitro CompoundsAmyloidogenic ProteinsDopamine1-Methyl-4-phenylpyridiniumProtein BindingNeurogenesisCognition DisordersHormesisBrain DiseasesSpinocerebellar DegenerationsNeurotoxicity SyndromesMagnetic Resonance ImagingScrapieAmino Acid SequenceWallerian Degenerationgamma-Synuclein1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineBrain ChemistryPC12 CellsMutant ProteinsMicrotubule-Associated ProteinsMitochondrial ProteinsProtein TransportOxidopamineInflammationNiemann-Pick Disease, Type CGreen Fluorescent ProteinsRats, Sprague-DawleySerine ProteasesGlutamic AcidInsomnia, Fatal FamilialDrosophilaBrain-Derived Neurotrophic FactorBlood-Brain BarrierPeptide FragmentsPhosphorylationMitochondrial DynamicsSilver StainingRotenoneThiolester HydrolasesAnalysis of VarianceBehavior, AnimalTime FactorsSpastic Paraplegia, HereditaryCytoprotectionProtein MultimerizationRNA, MessengerNeural Stem CellsProteolysisMicroscopy, Electron, TransmissionMotor ActivityPurkinje CellsMPTP PoisoningDisease ProgressionIntroversion (Psychology)Mutation, MissenseGroup III Histone DeacetylasesSynapsesProtein Structure, QuaternaryBiological MarkersOxidation-ReductionDNA-Binding ProteinsProteinsDrosophila melanogasterHEK293 CellsUbiquitin-Protein LigasesMesencephalonNeuritesNeuropsychological TestsQuinolinic AcidCycadophytaCaenorhabditis elegansProtein Structure, TertiaryStem Cell TransplantationGene ExpressionDrosophila ProteinsTyrosine 3-MonooxygenaseOligodendrogliaAphasia, Primary ProgressiveMyoclonic Epilepsies, ProgressiveIronMice, Neurologic MutantsNeuroimmunomodulationEnzyme InhibitorsHSP70 Heat-Shock ProteinsNeuritisTransfection
Neurodegenerative Diseases: 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.Nerve Degeneration: 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.Amyotrophic Lateral Sclerosis: 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)Neurons: 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.Alzheimer Disease: 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)tau Proteins: 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).Huntington Disease: 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)Brain: 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.Parkinson Disease: 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)alpha-Synuclein: A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.Nerve Tissue ProteinsTauopathies: 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.Neuroprotective Agents: 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.Disease Models, Animal: 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.Inclusion Bodies: 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)Heredodegenerative Disorders, Nervous System: Inherited disorders characterized by progressive atrophy and dysfunction of anatomically or physiologically related neurologic systems.Proteostasis Deficiencies: 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.Microglia: 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.Prions: 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.Prion Diseases: 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)Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Synucleins: 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.Amyloid beta-Peptides: 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.Spinocerebellar Ataxias: 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)Frontotemporal Lobar Degeneration: 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.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.Oxidative Stress: 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).Mutation: 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.Trinucleotide Repeat Expansion: 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.Frontotemporal Dementia: 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.Friedreich Ataxia: 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)Mitochondria: 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)Autophagy: 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.Neuronal Ceroid-Lipofuscinoses: 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.Guam: 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)Amyloid: 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.Aging: The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.Dementia: 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.Protein Folding: Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.Cells, Cultured: 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.Neurofibrillary Tangles: 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.Lewy Body 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)Astrocytes: 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.Peptides: 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.Neurotoxins: 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.Parkinsonian Disorders: 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.Superoxide Dismutase: 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 1.15.1.1.Mice, Inbred C57BLModels, Biological: 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.Lewy Bodies: 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.Axonal Transport: 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)Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.Trinucleotide Repeats: Microsatellite repeats consisting of three nucleotides dispersed in the euchromatic arms of chromosomes.Motor Neuron Disease: 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)Supranuclear Palsy, Progressive: 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)Mitochondrial Diseases: 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.Motor Neurons: Neurons which activate MUSCLE CELLS.Ubiquitin: 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.Central Nervous System Diseases: Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord.Hippocampus: 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.Cycas: 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.Iron-Binding Proteins: Proteins that specifically bind to IRON.Proteasome Endopeptidase Complex: 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.Muscular Atrophy, Spinal: 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)Cerebral Cortex: 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.Pick Disease of the Brain: 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)Signal Transduction: 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.Cell Survival: 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.RNA-Binding Protein FUS: 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.Neuroglia: 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.Gliosis: The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion.Apoptosis: 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.Gene Expression Regulation: 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.Nervous System Diseases: 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.Plaque, Amyloid: Accumulations of extracellularly deposited AMYLOID FIBRILS within tissues.Reactive Oxygen Species: 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.Multiple System Atrophy: 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)Nuclear Proteins: 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, Genetically Modified: ANIMALS whose GENOME has been altered by GENETIC ENGINEERING, or their offspring.Substantia Nigra: 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.Molecular Chaperones: 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.PrPSc Proteins: 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).Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.beta-Synuclein: 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.Rotarod Performance Test: 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.Amino Acids, DiaminoParkinson Disease, Secondary: 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)Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body.Intranuclear Inclusion Bodies: Circumscribed masses of foreign or metabolically inactive materials, within the CELL NUCLEUS. Some are VIRAL INCLUSION BODIES.DNA Repeat Expansion: An increase number of repeats of a genomic, tandemly repeated DNA sequence from one generation to the next.Spinal Cord: A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.Dopaminergic Neurons: Neurons whose primary neurotransmitter is DOPAMINE.Atrophy: 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.Blotting, Western: 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.Corpus Striatum: 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.TDP-43 Proteinopathies: 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.Antioxidants: 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.Cyclin-Dependent Kinase 5: 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.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Neurofilament Proteins: 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)Amyloid beta-Protein Precursor: 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.Neuroaxonal Dystrophies: 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)Ataxia: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Encephalitis: 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.PrPC Proteins: 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.Trauma, Nervous System: Traumatic injuries to the brain, cranial nerves, spinal cord, autonomic nervous system, or neuromuscular system, including iatrogenic injuries induced by surgical procedures.Creutzfeldt-Jakob Syndrome: 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))Cerebellum: 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.Molecular Sequence Data: 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.Mice, Knockout: 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.Glial Fibrillary Acidic Protein: An intermediate filament protein found only in glial cells or cells of glial origin. MW 51,000.Machado-Joseph Disease: 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)Lysosomes: 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)Nitro Compounds: Compounds having the nitro group, -NO2, attached to carbon. When attached to nitrogen they are nitramines and attached to oxygen they are NITRATES.Amyloidogenic Proteins: 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.Dopamine: 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.1-Methyl-4-phenylpyridinium: 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.Protein Binding: 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.Neurogenesis: Formation of NEURONS which involves the differentiation and division of STEM CELLS in which one or both of the daughter cells become neurons.Cognition Disorders: Disturbances in mental processes related to learning, thinking, reasoning, and judgment.Hormesis: 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.Brain Diseases: 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.Spinocerebellar Degenerations: 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.Neurotoxicity Syndromes: 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.Magnetic Resonance Imaging: 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.Scrapie: 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.Amino Acid Sequence: 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.Wallerian Degeneration: 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.gamma-Synuclein: 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-1.1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: A dopaminergic neurotoxic compound which produces irreversible clinical, chemical, and pathological alterations that mimic those found in Parkinson disease.Brain Chemistry: 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.PC12 Cells: 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.Mutant Proteins: Proteins produced from GENES that have acquired MUTATIONS.Microtubule-Associated Proteins: 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.Mitochondrial Proteins: Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.Protein Transport: 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.Oxidopamine: 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.Inflammation: 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.Niemann-Pick Disease, Type C: 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.Green Fluorescent Proteins: 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.Rats, Sprague-Dawley: 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.Serine Proteases: Peptide hydrolases that contain at the active site a SERINE residue involved in catalysis.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.Insomnia, Fatal Familial: An autosomal dominant disorder characterized by degeneration of the THALAMUS and progressive insomnia. It is caused by a mutation in the prion protein (PRIONS).Drosophila: 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.Brain-Derived Neurotrophic Factor: 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)Blood-Brain Barrier: 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.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Mitochondrial Dynamics: The continuous remodeling of MITOCHONDRIA shape by fission and fusion in response to physiological conditions.Silver Staining: The use of silver, usually silver nitrate, as a reagent for producing contrast or coloration in tissue specimens.Rotenone: A botanical insecticide that is an inhibitor of mitochondrial electron transport.Thiolester HydrolasesAnalysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.Behavior, Animal: The observable response an animal makes to any situation.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Spastic Paraplegia, Hereditary: 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)Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents.Protein Multimerization: The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.RNA, Messenger: 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.Neural Stem Cells: 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.Proteolysis: 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.Microscopy, Electron, Transmission: Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.Motor Activity: The physical activity of a human or an animal as a behavioral phenomenon.Purkinje Cells: The output neurons of the cerebellar cortex.MPTP Poisoning: 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)Disease Progression: 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.Introversion (Psychology): A state in which attention is largely directed inward upon one's self.Mutation, Missense: 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)Group III Histone Deacetylases: A subclass of histone deacetylases that are NAD-dependent. Several members of the SIRTUINS family are included in this subclass.Synapses: 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.Protein Structure, Quaternary: The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).Biological Markers: 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.Oxidation-Reduction: 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).DNA-Binding Proteins: 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.Proteins: 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.Drosophila melanogaster: A species of fruit fly much used in genetics because of the large size of its chromosomes.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Ubiquitin-Protein Ligases: 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.Mesencephalon: 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.Neurites: 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.Neuropsychological Tests: 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.Quinolinic Acid: 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.Cycadophyta: 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.Caenorhabditis elegans: A species of nematode that is widely used in biological, biochemical, and genetic studies.Protein Structure, Tertiary: 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.Stem Cell Transplantation: 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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Drosophila Proteins: 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.Tyrosine 3-Monooxygenase: An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC 1.14.16.2.Oligodendroglia: 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.Aphasia, Primary Progressive: 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)Myoclonic Epilepsies, Progressive: 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.Iron: 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, Neurologic Mutants: Mice which carry mutant genes for neurologic defects or abnormalities.Neuroimmunomodulation: The biochemical and electrophysiological interactions between the NERVOUS SYSTEM and IMMUNE SYSTEM.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.HSP70 Heat-Shock Proteins: 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.Neuritis: A general term indicating inflammation of a peripheral or cranial nerve. Clinical manifestation may include PAIN; PARESTHESIAS; PARESIS; or HYPESTHESIA.Transfection: 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.

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)

EU Joint Programme - Neurodegenerative Disease Research (JPND) | National Science CentreEU Joint Programme - Neurodegenerative Disease Research (JPND) | National Science Centre
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:. ...
Distinct subcortical atrophy patterns across four different neurodegenerative syndromesDistinct subcortical atrophy patterns across four different neurodegenerative syndromes
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 ...
Quantification of total apolipoprotein E and its isoforms in cerebrospinal fluid from patients with neurodegenerative diseases ...Quantification of total apolipoprotein E and its isoforms in cerebrospinal fluid from patients with neurodegenerative diseases ...
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
Ubiquitin-independent function of optineurin in autophagic clearance of protein aggregates | Journal of Cell ScienceUbiquitin-independent function of optineurin in autophagic clearance of protein aggregates | Journal of Cell Science
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 ...
Role of Platelets in Neurodegenerative Diseases: A Universal Pathophysiology.Role of Platelets in Neurodegenerative Diseases: A Universal Pathophysiology.
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
HKU Scholars Hub: A Pharmacological Appraisal of Neuroprotective and Neurorestorative Flavonoids Against Neurodegenerative...HKU Scholars Hub: A Pharmacological Appraisal of Neuroprotective and Neurorestorative Flavonoids Against Neurodegenerative...
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 ...
NEAT1 and Paraspeckles in Neurodegenerative Diseases: A Missing Lnc Found? - PubMedNEAT1 and Paraspeckles in Neurodegenerative Diseases: A Missing Lnc Found? - PubMed
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 …
Neurodegenerative Disorders as Systemic Diseases :: E-book CollectionNeurodegenerative Disorders as Systemic Diseases :: E-book Collection
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 Disease | Research | USCNeurodegenerative Disease | Research | USC
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 DiseasesNeurodegenerative 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 ...
IJMS | Free Full-Text | Oxidative Stress and Neurodegenerative Disorders | HTMLIJMS | Free Full-Text | Oxidative Stress and Neurodegenerative Disorders | HTML
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,
JLR: Thematic series highlights Alzheimers greatest genetic risk factor, ApoEJLR: Thematic series highlights Alzheimer's greatest genetic risk factor, ApoE
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 ...
New Biomarkers Could Help Doctors Spot Alzheimers and Other Neurodegenerative Diseases | EmaxHealthNew Biomarkers Could Help Doctors Spot Alzheimer's and Other Neurodegenerative Diseases | EmaxHealth
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 ...
IIT Gandhinagar Postdoc Openings in Intracellular Transport/Human Diseases ~ helpBIOTECHIIT Gandhinagar Postdoc Openings in Intracellular Transport/Human Diseases ~ helpBIOTECH
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 ...
Brain Discovery Explains A Great Mystery of Alzheimers and Parkinsons - Neuroscience NewsBrain Discovery Explains A Great Mystery of Alzheimer's and Parkinson's - Neuroscience News
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. ...
Calcium Signaling | Leaders in Pharmaceutical Business Intelligence (LPBI) GroupCalcium Signaling | Leaders in Pharmaceutical Business Intelligence (LPBI) Group
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 ...
Cannabinoids and Neurodegenerative Diseases | Bentham ScienceCannabinoids and Neurodegenerative Diseases | Bentham Science
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 ...
Huntingtons disease - Vegsource.comHuntington's disease - Vegsource.com
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,....... ...
A Microfluidic Brain Interface for In Vivo Recording of Neurochemical ActivityA Microfluidic Brain Interface for In Vivo Recording of Neurochemical Activity
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 - Vegsource.comLou Gehrig's disease - Vegsource.com
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,....... ...
Fluorescent HTS Assay for Methyltransferases in Neurodegenerative Diseases | SBIR.govFluorescent HTS Assay for Methyltransferases in Neurodegenerative Diseases | SBIR.gov
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 ...
NeuroTherapyNeuroTherapy
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.
New biotech firm launched to find treatments for neurodegenerative diseases on NewsHub.orgNew biotech firm launched to find treatments for neurodegenerative diseases on NewsHub.org
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 NewsHub.org
P53 Dysfunction in Neurodegenerative Diseases - The Cause or Effect of Pathological Changes?P53 Dysfunction in Neurodegenerative Diseases - The Cause or Effect of Pathological Changes?
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 ...
Cytokine/neurotrophin interaction in the aged central nervous system<...Cytokine/neurotrophin interaction in the aged central nervous system<...
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 ...
Translational Therapeutics LaboratoryTranslational Therapeutics Laboratory
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 ...
Discovery of N -cyclobutylaminoethoxyisoxazole derivatives as novel sigma-1 receptor ligands with neurite outgrowth efficacy in...Discovery of N -cyclobutylaminoethoxyisoxazole derivatives as novel sigma-1 receptor ligands with neurite outgrowth efficacy in...
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 ...
New ALS Research Study | MassGeneral Institute for Neurodegenerative DiseaseNew ALS Research Study | MassGeneral Institute for Neurodegenerative Disease
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.. ...
Dr Guillaume Hautbergue MSc PhD - Staff - Neuroscience - The University of SheffieldDr Guillaume Hautbergue MSc PhD - Staff - Neuroscience - The University of Sheffield
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 ...
Nna Proteins Play Role in Catastrophic Neuron Death in Mice, Flies - And Perhaps PeopleNna Proteins Play Role in Catastrophic Neuron Death in Mice, Flies - And Perhaps People
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.
Contribution of Yeast Models to Neurodegeneration ResearchContribution of Yeast Models to Neurodegeneration Research
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
Helmholtz Zentrum München Elucidates a Molecular Mechanism contributing to Neuronal Circuit Formation - Healthcanal.com :...Helmholtz Zentrum München Elucidates a Molecular Mechanism contributing to Neuronal Circuit Formation - Healthcanal.com :...
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 ...
Hybridtides: Stable Linear Peptides and Their Use in Harnessing the Adaptive Immune System to Treat Neurodegenerative Disorders...Hybridtides: Stable Linear Peptides and Their Use in Harnessing the Adaptive Immune System to Treat 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
Biometals in Neurodegenerative Diseases : Mechanisms and TherapeuticsBiometals in Neurodegenerative Diseases : Mechanisms and Therapeutics
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 ...
Radiographic and Intravascular (IVUS) Evaluation of Venous Morphology During CCSVI Treatment - Full Text View - ClinicalTrials...Radiographic and Intravascular (IVUS) Evaluation of Venous Morphology During CCSVI Treatment - Full Text View - ClinicalTrials...
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 ...
Measurement of apolipoprotein E and amyloid β clearance rates in the mouse brain using bolus stable isotope labeling |...Measurement of apolipoprotein E and amyloid β clearance rates in the mouse brain using bolus stable isotope labeling |...
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
Autoimmune Features of Neurodegenerative Disorders - Full Text View - ClinicalTrials.govAutoimmune Features of Neurodegenerative Disorders - Full Text View - ClinicalTrials.gov
Neurodegenerative diseases are characterized by the misprocessing of specific proteins, but how and if this results in cell death is unknown. This study is being conducted to better understand the role of inflammation in Parkinsons disease (PD) and Alzheimers disease (AD). Both AD and PD have long been known to feature prominent neuroinflammatory components. Preliminary studies have found autoimmune features in several patients including recognition of self-antigens by specific T cells. This study will test the hypothesis that AD and PD are associated with self-derived antigens (alpha-syn and tau protein) that become recognized by T cells during aging and disease. The overall aim is to identify antigenic responses associated with PD and AD. The specific aims include:. ...
Neurodegenerative Diseases - Home - Karger PublishersNeurodegenerative Diseases - Home - Karger Publishers
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
Cupid Project Home | CuPiDCupid Project Home | CuPiD
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.. ...
Cupid Project Home | CuPiDCupid Project Home | CuPiD
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.. ...
Mechanisms of Cellular Death in Neurodegeneration (MCDN) - Weston Brain InstituteMechanisms of Cellular Death in Neurodegeneration (MCDN) - Weston Brain Institute
All proposals must clearly and explicitly describe whether specific hypotheses are to be investigated, the program of work, the methods for study, sample, outcomes, etc. The ultimate goal is to increase the understanding and knowledge of mechanisms of brain cell death in neurodegenerative diseases and develop novel model systems for further investigations.. Given the magnitude and complexity of the scientific challenge, the MCDN Initiative strongly encourages submissions from global collaborative research teams that exemplify interdisciplinary expertise. In addition, while novel and creative ideas are sought, proposals also need to demonstrate feasibility. The funding organizations recognize the need to increase the range and diversity of scientific disciplines that might offer innovative techniques or solutions, and researchers that may not have a history of research in neurodegenerative diseases are encouraged to apply, especially as members of consortia that have disease expertise.. ...
Dr. Sexy President - NeurodegenerativeDr. Sexy President - Neurodegenerative
Aim of the Dresden site of the German Centre for Neurodegenerative Diseases is to make use of insights from stem cell research and developmental biology for prevention and therapy of neurodegenerative diseases. Biologically sound strategies for recruiting endogenous potentials for compensation and regeneration will be developed.. Why does physical and mental activity provide a certain degree of protection against dementia and neurodegeneration ? Physical activity especially is one of the few scientifically proven methods available to the individual to reduce the risk of neurodegenerative disease and influence its progression positively. Where is the link between neurodegeneration and brain development ? How does the brain combat degenerative processes? Are there any simple ways to boost this potential in preventing, compensating for and treating such disease ?. Throughout a persons life, the brain is in a constant state of change and its structure is directly related to its function. This ...
Drosophila as an Animal Model for Neurodegenerative DiseasesDrosophila as an Animal Model for Neurodegenerative Diseases
The goal: Understanding the etiology and pathogenesis of neurodegenerative diseases without the ethical problems often associated with vertebrate animal models. These projects are done in collaboration with medical-oriented groups. Behavior turns out to be a useful and sensitive early indicator of neurodegenerative processes in the nervous system of flies. In several different studies we could prove that behavioral parameters went bad long before neurodegeneration became manifest in neuroanatomical preparations. ...
Mitochondrial Disorders of the Nuclear Genome - PubMedMitochondrial Disorders of the Nuclear Genome - PubMed
Future developments will show that many neurodegenerative disorders are due to mutations of nuclear genes controlling mitochondrial function, fusion and fission.
A model of neurodegenerationA model of neurodegeneration
This research could be very important for us if the model of neurodegeneration / axonal degeneration that they have developed applies to MS. New Pathway is a Common Thread in Age-Related Neurodegenerative Diseases January 29, 2009 - How are neurodegenerative ...
A new cellular garbage control pathway with relevance for human neurodegenerative diseases - Healthcanal.com : Healthcanal.comA new cellular garbage control pathway with relevance for human neurodegenerative diseases - Healthcanal.com : Healthcanal.com
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 ...
Quantitative measurement of postural sway in mouse models of human neurodegenerative disease<...Quantitative measurement of postural sway in mouse models of human neurodegenerative disease<...
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 ...
Glycine-alanine dipeptide repeats spread rapidly in a repeat length- and age-dependent manner in the fly brain | Acta...Glycine-alanine dipeptide repeats spread rapidly in a repeat length- and age-dependent manner in the fly brain | Acta...
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
VCP provides new insights into motor neuron disease and dementia | Degenerating neuronsVCP provides new insights into motor neuron disease and dementia | Degenerating neurons
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…
Brain Changes in Iron Loading DisordersBrain Changes in Iron Loading Disorders
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 ...
Plus itPlus it
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 ...
Images for gaba receptorImages for gaba receptor
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 ...
Cancer - Part 2Cancer - Part 2
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. ...
Transposable Elements in TDP-43-Mediated Neurodegenerative Disorders - CSHL Scientific Digital RepositoryTransposable Elements in TDP-43-Mediated Neurodegenerative Disorders - CSHL Scientific Digital Repository
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.. ...
Deep Brain Stimulation May Improve Cognition in Dementia, Other Neurodegenerative DiseasesDeep Brain Stimulation May Improve Cognition in Dementia, Other 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.
A new perspective for advanced positron emission tomography-based molecular imaging in neurodegenerative proteinopathies -...A new perspective for advanced positron emission tomography-based molecular imaging in neurodegenerative proteinopathies -...
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 ...
Young Scientists JournalYoung Scientists Journal
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 role of lipids in autophagy and its implication in neurodegenerationThe 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
Follow ME in Denmark: Toll like receptors (TLR) and MEFollow ME in Denmark: Toll like receptors (TLR) and ME
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 ...
T-cells Show Promise for ALS, Neurodegenerative Disease Therapies | Neurodegenerative Diseases | Disease and ConditionsT-cells Show Promise for ALS, Neurodegenerative Disease Therapies | Neurodegenerative Diseases | Disease and Conditions
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.
A New Study Suggests THCA May Treat Neurodegenerative and Neuroinflammatory Diseases - Cannabis in AustraliaA New Study Suggests THCA May Treat Neurodegenerative and Neuroinflammatory Diseases - Cannabis in Australia
According to a new study, tetrahydrocannabinolic acid (THCA), a compound found in cannabis, may be useful in treating neurodegenerative and neuroinflammatory diseases.
Treatment of Central Nervous System Degenerative Disorders | Goodman and Gilmans Manual of Pharmacology and Therapeutics, 2e |...Treatment of Central Nervous System Degenerative Disorders | Goodman and Gilman's Manual of Pharmacology and Therapeutics, 2e |...
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 ...
Improving brains garbage disposal may slow Alzheimers and other neurodegenerative diseases | EurekAlert! Science NewsImproving brain's garbage disposal may slow Alzheimer's and other neurodegenerative diseases | EurekAlert! Science News
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.
talks.cam : Neurons Put Out the Trash: A Novel Facet of Proteostasis and Mitochondrial Quality Controltalks.cam : Neurons Put Out the Trash: A Novel Facet of Proteostasis and Mitochondrial Quality Control
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 ...
ReferencesReferences
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 ...
News | Johns Hopkins PathologyNews | Johns Hopkins Pathology
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 ...
Frontiers | Bile Acids in Neurodegenerative Disorders | Frontiers in Aging NeuroscienceFrontiers | Bile Acids in Neurodegenerative Disorders | Frontiers in Aging Neuroscience
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.
beasiswa] [info] 8 PhD scholarships sponsored by the German Research Center for Neurodegenerative Diseases (DZNE) - Beasiswabeasiswa] [info] 8 PhD scholarships sponsored by the German Research Center for Neurodegenerative Diseases (DZNE) - Beasiswa
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 ...
Myriam Heiman | Picower InstituteMyriam Heiman | Picower Institute
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 ...
Unlocking the Mystery of Tau for Treatment of Neurodegenerative DiseasesUnlocking the Mystery of Tau for Treatment of Neurodegenerative Diseases
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…
Joseph R Mazzulli, PhD : Faculty Profile: The Ken & Ruth Davee Department of Neurology: Feinberg School of Medicine:...Joseph R Mazzulli, PhD : Faculty Profile: The Ken & Ruth Davee Department of Neurology: Feinberg School of Medicine:...
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 ...
Alzheimer - Genesis Health ServicesAlzheimer - Genesis Health Services
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 ...
Environmental Factor: October 2007: Extramural Papers of the MonthEnvironmental Factor: October 2007: Extramural Papers of the Month
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 Trial Registries | ALZFORUMClinical Trial Registries | ALZFORUM
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 ...
Neurofilament light | Pathogenes IncNeurofilament light | Pathogenes Inc
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 ...
AT-1 is the ER membrane acetyl-CoA transporter and is essential for cell viability | Journal of Cell ScienceAT-1 is the ER membrane acetyl-CoA transporter and is essential for cell viability | Journal of Cell Science
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 ...
ALZFORUM | NETWORKING FOR A CUREALZFORUM | NETWORKING FOR A CURE
The implications of this study for aging of the brain as well as for neurodegenerative disorders are potentially profound. The postulated link between brain aging and the aging of nuclear pore proteins is intriguing. For Alzheimer disease, concepts of pathogenesis are increasingly focusing on targets alternative to, or upstream of, β amyloid deposition. Critical events in the cell nucleus have garnered well-deserved attention in this regard. Histone deacetylases, transcriptional regulation, and DNA repair have taken center stage. The study by Hetzers group brings the nuclear pores, the gateway to the nucleus, into the mix. Particularly provocative is the implication that aged and/or oxidatively damaged leaky pores allow the ectopic nuclear localization of cytoplasmic proteins, in this case, class III β tubulin. Could this represent a detrimental consequence of age-associated nuclear pore dysfunction? Do the intranuclear tubulin aggregates that form in "leaky" nuclei negatively influence ...
IJMS | Free Full-Text | High-Throughput Screening Methodology to Identify Alpha-Synuclein Aggregation InhibitorsIJMS | Free Full-Text | High-Throughput Screening Methodology to Identify Alpha-Synuclein Aggregation Inhibitors
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
Frontiers | The Role of Microglia in Retinal Neurodegeneration: Alzheimers Disease, Parkinson, and Glaucoma | Frontiers in...Frontiers | The Role of Microglia in Retinal Neurodegeneration: Alzheimer's Disease, Parkinson, and Glaucoma | Frontiers in...
Microglia, the immunocompetent cells of the central nervous system (CNS), act as neuropathology sensors and are neuroprotective under physiological conditions. Microglia react to injury and degeneration with immune-phenotypic and morphological changes, proliferation, migration, and inflammatory cytokine production. An uncontrolled microglial response secondary to sustained CNS damage can put neuronal survival at risk due to excessive inflammation. A neuroinflammatory response is considered among the etiological factors of the major aged-related neurodegenerative diseases of the CNS, and microglial cells are key players in these neurodegenerative lesions. The retina is an extension of the brain and therefore the inflammatory response in the brain can occur in the retina. The brain and retina are affected in several neurodegenerative diseases, including Alzheimers disease (AD), Parkinsons disease (PD), and glaucoma. AD is an age-related neurodegeneration of the CNS characterized by neuronal and synaptic
Environmental Factors in Neurodevelopmental and Neurodegenerative Disorders - Google BooksEnvironmental Factors in Neurodevelopmental and Neurodegenerative Disorders - Google Books
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
How to reprogram human fibroblasts to neurons | Cell & Bioscience | Full TextHow to reprogram human fibroblasts to neurons | Cell & Bioscience | Full Text
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
Physiology, Neurotransmitters Article - StatPearlsPhysiology, Neurotransmitters Article - StatPearls
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 ...
Peripheral Protein Profile As A Biological Marker For Neurodegenerative DiseasesPeripheral Protein Profile As A Biological Marker For Neurodegenerative Diseases
Neurodegenerative diseases such as Alzheimer�s disease (AD) and Parkinson�s disease (PD) are currently considered as protein misfolding diseases. Determina...
neurodegenerative diseases Archives - Page 3 of 83 - Neuroscience Newsneurodegenerative diseases Archives - Page 3 of 83 - Neuroscience News
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... ...
Scripps Research- News & Views,Scientists Find Way to Block Stress-Related Cell DeathScripps Research- News & Views,Scientists Find Way to Block Stress-Related Cell Death
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 ...
Patient ResourcesPatient Resources
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.. ...
Looking Back at the History of Alzheimers Research - MD Magazine features MGH investigator Rudolph Tanzi | MassGeneral...Looking Back at the History of Alzheimer's Research - MD Magazine features MGH investigator Rudolph Tanzi | MassGeneral...
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.. ...
Roles of sigma-1 receptors on mitochondrial functions relevant to neurodegenerative diseases | Journal of Biomedical Science |...Roles of sigma-1 receptors on mitochondrial functions relevant to neurodegenerative diseases | Journal of Biomedical Science |...
The sigma-1 receptor (Sig-1R) is a chaperone that resides mainly at the mitochondrion-associated endoplasmic reticulum (ER) membrane (called the MAMs) and acts as a dynamic pluripotent modulator in living systems. At the MAM, the Sig-1R is known to play a role in regulating the Ca2+ signaling between ER and mitochondria and in maintaining the structural integrity of the MAM. The MAM serves as bridges between ER and mitochondria regulating multiple functions such as Ca2+ transfer, energy exchange, lipid synthesis and transports, and protein folding that are pivotal to cell survival and defense. Recently, emerging evidences indicate that the MAM is critical in maintaining neuronal homeostasis. Thus, given the specific localization of the Sig-1R at the MAM, we highlight and propose that the direct or indirect regulations of the Sig-1R on mitochondrial functions may relate to neurodegenerative diseases including Alzheimers disease (AD), Parkinsons disease (PD), Huntingtons disease (HD) and amyotrophic
DMOZ - Health: Conditions and Diseases: Neurological Disorders: Neurodegenerative Diseases: AlpersDMOZ - Health: Conditions and Diseases: Neurological Disorders: Neurodegenerative Diseases: Alpers'
Alpers disease or Alpers Progressive Infantile Poliodystrophy is a rare, progressive neurodegenerative disease of the brain. It is thought to be an autosomal recessive disorder and usually affects children under the age of 5. Convulsions mark the onset of the disease, followed by dementia, spasticity and monoclonus. The untreatable disease is fatal and patients usually die a few months after disease onset.
New understanding of Jekyll and Hyde brain cells | Keep It CleverNew understanding of 'Jekyll and Hyde' brain cells | Keep It Clever
New research has shown how normally helpful brain cells can turn rogue and kill off other brain cells following injury or disease.. The brain cells, known as astrocytes, have long been implicated in the pathology of a range of human neurodegenerative diseases or injuries including Alzheimers, Huntingtons and Parkinsons disease, brain trauma and spinal cord injury.. Now a new study led by researchers at The University of Melbourne and Stanford University provides an understanding of the mechanism involved and for the first time provides hope that a lot of these diseases may in fact be treatable.. Researcher Dr Shane Liddelow from the University of Melbournes Department of Pharmacology and Therapeutics, and the Department of Neurobiology at Stanford University, said astrocytes are often characterised as helper cells.. But he noted they can also contribute to damage caused by brain injury and disease by turning toxic and killing other types of brain cells.. "These apparently opposing effects ...
The Molecular and Clinical Pathology of Neurodegenerative DiseaseThe Molecular and Clinical Pathology of Neurodegenerative Disease
... brings together in one volume our current understanding of the molecular basis of neurodegeneration...
Alzheimers Disease research at JAXAlzheimer's Disease research at JAX
An age-related neurodegenerative disease, Alzheimers is the leading cause of dementia among people 65 and older. Scientists at the Jackson Laboratory are developing new mouse models to study Alzheimers.
CDR computerized assessment systemCDR computerized assessment system
Hermona SoreqHermona Soreq
RadequinilRadequinil
Amyloid betaAmyloid beta
RaseglurantRaseglurant
Heart-type fatty acid binding proteinHeart-type fatty acid binding protein
Keith LawsKeith Laws
STH (gene)STH (gene)
DysprosodyDysprosody
LRP1LRP1
Amyloid precursor proteinAmyloid precursor protein
Cell therapyCell therapy
NicastrinNicastrin
Stress granuleStress granule
Embryonic stem cellEmbryonic stem cell
DrinabantDrinabant
Florbetaben (18F)Florbetaben (18F)
Beta-secretase 1Beta-secretase 1
Regressive autismRegressive autism
Protein aggregationProtein aggregation
Anne B. YoungAnne B. Young
SynucleinSynuclein
David PerlmutterDavid Perlmutter
Bleomycin hydrolaseBleomycin hydrolase
AzollaAzolla
PRNPPRNP
Retinal degeneration (rhodopsin mutation)Retinal degeneration (rhodopsin mutation)
TocopherolTocopherol
AloracetamAloracetam
Protein disulfide-isomeraseProtein disulfide-isomerase
CyanotoxinCyanotoxin
TATA boxTATA box
Cold Spring Harbor LaboratoryCold Spring Harbor Laboratory
FastingFasting
Flight attendantFlight attendant
Mark A. SmithMark A. Smith
배아줄기세포 - 위키백과, 우리 모두의 백과사전배아줄기세포 - 위키백과, 우리 모두의 백과사전
Brain-derived neurotrophic factorBrain-derived neurotrophic factor
BiomarkerBiomarker
Olfactory ensheathing cellsOlfactory ensheathing cells
Amyotrophic lateral sclerosisAmyotrophic lateral sclerosis
ProteasomeProteasome
TetrahydrocannabinolTetrahydrocannabinol
Beta-amiloide, a enciclopedia libreBeta-amiloide, a enciclopedia libre
LIG3, a enciclopedia libreLIG3, a enciclopedia libre
Ubikinon - Wikipedija, prosta enciklopedijaUbikinon - Wikipedija, prosta enciklopedija
AutophagyAutophagy
AutophagyAutophagy
Lewy bodyLewy body
Epigenetics of neurodegenerative diseasesEpigenetics of neurodegenerative diseases
PRNPPRNP
Tirozin 3-monooksigenaza - Википедија, слободна енциклопедијаTirozin 3-monooksigenaza - Википедија, слободна енциклопедија
Progressive supranuclear palsyProgressive supranuclear palsy
EpigeneticsEpigenetics
SoursopSoursop
Medical geneticsMedical genetics
Tahikininski receptor 1 - ВикипедијаTahikininski receptor 1 - Википедија
Demyelinating diseaseDemyelinating disease
Parkinsons diseaseParkinson's disease
StimulantStimulant
AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPsychiatry and PsychologyPhenomena and ProcessesDisciplines and OccupationsInformation ScienceHealth CareGeographicals
Neurodegenerative DiseasesNerve DegenerationAmyotrophic Lateral SclerosisNeuronsAlzheimer Diseasetau ProteinsHuntington DiseaseBrainParkinson Diseasealpha-SynucleinNerve Tissue ProteinsTauopathiesNeuroprotective AgentsDisease Models, AnimalInclusion BodiesHeredodegenerative Disorders, Nervous SystemProteostasis DeficienciesMicrogliaPrionsPrion DiseasesMice, TransgenicSynucleinsAmyloid beta-PeptidesSpinocerebellar AtaxiasFrontotemporal Lobar DegenerationCell DeathOxidative StressMutationTrinucleotide Repeat ExpansionFrontotemporal DementiaFriedreich AtaxiaMitochondriaAutophagyNeuronal Ceroid-LipofuscinosesGuamAmyloidAgingDementiaProtein FoldingCells, CulturedNeurofibrillary TanglesLewy Body DiseaseAstrocytesPeptidesNeurotoxinsParkinsonian DisordersSuperoxide DismutaseMice, Inbred C57BLModels, BiologicalLewy BodiesAxonal TransportCentral Nervous SystemTrinucleotide RepeatsMotor Neuron DiseaseSupranuclear Palsy, ProgressiveMitochondrial DiseasesMotor NeuronsUbiquitinCentral Nervous System DiseasesHippocampusCycasIron-Binding ProteinsProteasome Endopeptidase ComplexMuscular Atrophy, SpinalCerebral CortexPick Disease of the BrainSignal TransductionCell SurvivalRNA-Binding Protein FUSNeurogliaGliosisApoptosisGene Expression RegulationNervous System DiseasesPlaque, AmyloidReactive Oxygen SpeciesMultiple System AtrophyNuclear ProteinsAnimals, Genetically ModifiedSubstantia NigraMolecular ChaperonesPrPSc ProteinsImmunohistochemistrybeta-SynucleinRotarod Performance TestAmino Acids, DiaminoParkinson Disease, SecondaryAxonsIntranuclear Inclusion BodiesDNA Repeat ExpansionSpinal CordDopaminergic NeuronsAtrophyBlotting, WesternCorpus StriatumTDP-43 ProteinopathiesAntioxidantsCyclin-Dependent Kinase 5PhenotypeNeurofilament ProteinsAmyloid beta-Protein PrecursorNeuroaxonal DystrophiesAtaxiaCell LineEncephalitisPrPC ProteinsTrauma, Nervous SystemCreutzfeldt-Jakob SyndromeCerebellumMolecular Sequence DataMice, KnockoutGlial Fibrillary Acidic ProteinMachado-Joseph DiseaseLysosomesNitro CompoundsAmyloidogenic ProteinsDopamine1-Methyl-4-phenylpyridiniumProtein BindingNeurogenesisCognition DisordersHormesisBrain DiseasesSpinocerebellar DegenerationsNeurotoxicity SyndromesMagnetic Resonance ImagingScrapieAmino Acid SequenceWallerian Degenerationgamma-Synuclein1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineBrain ChemistryPC12 CellsMutant ProteinsMicrotubule-Associated ProteinsMitochondrial ProteinsProtein TransportOxidopamineInflammationNiemann-Pick Disease, Type CGreen Fluorescent ProteinsRats, Sprague-DawleySerine ProteasesGlutamic AcidInsomnia, Fatal FamilialDrosophilaBrain-Derived Neurotrophic FactorBlood-Brain BarrierPeptide FragmentsPhosphorylationMitochondrial DynamicsSilver StainingRotenoneThiolester HydrolasesAnalysis of VarianceBehavior, AnimalTime FactorsSpastic Paraplegia, HereditaryCytoprotectionProtein MultimerizationRNA, MessengerNeural Stem CellsProteolysisMicroscopy, Electron, TransmissionMotor ActivityPurkinje CellsMPTP PoisoningDisease ProgressionIntroversion (Psychology)Mutation, MissenseGroup III Histone DeacetylasesSynapsesProtein Structure, QuaternaryBiological MarkersOxidation-ReductionDNA-Binding ProteinsProteinsDrosophila melanogasterHEK293 CellsUbiquitin-Protein LigasesMesencephalonNeuritesNeuropsychological TestsQuinolinic AcidCycadophytaCaenorhabditis elegansProtein Structure, TertiaryStem Cell TransplantationGene ExpressionDrosophila ProteinsTyrosine 3-MonooxygenaseOligodendrogliaAphasia, Primary ProgressiveMyoclonic Epilepsies, ProgressiveIronMice, Neurologic MutantsNeuroimmunomodulationEnzyme InhibitorsHSP70 Heat-Shock ProteinsNeuritisTransfection
Neurodegenerative DiseasesNeurodegenerative Diseases
Proteomic Analysis of Mitochondrial Dysfunction in Neurodegenerative DiseaseProteomic Analysis of Mitochondrial Dysfunction in Neurodegenerative Disease
Cutting calories may help prevent neurodegenerative diseases - UPI.comCutting calories may help prevent neurodegenerative diseases - UPI.com
Neurodegenerative Diseases - Home - Karger PublishersNeurodegenerative Diseases - Home - Karger Publishers
Pregnancy Exercises Protect Offspring Against Neurodegenerative DiseasesPregnancy Exercises Protect Offspring Against Neurodegenerative Diseases
Fluorescent HTS Assay for Methyltransferases in Neurodegenerative Diseases | SBIR.govFluorescent HTS Assay for Methyltransferases in Neurodegenerative Diseases | SBIR.gov
Corrected Protein Structure Reveals Drug Targets for Cancer, Neurodegenerative DiseasesCorrected Protein Structure Reveals Drug Targets for Cancer, Neurodegenerative Diseases
Citation Machine: Neurodegenerative Diseases format citation generator for websiteCitation Machine: Neurodegenerative Diseases format citation generator for website
Role of Platelets in Neurodegenerative Diseases: A Universal Pathophysiology.Role of Platelets in Neurodegenerative Diseases: A Universal Pathophysiology.
New Biomarkers Could Help Doctors Spot Alzheimers and Other Neurodegenerative Diseases | EmaxHealthNew Biomarkers Could Help Doctors Spot Alzheimer's and Other Neurodegenerative Diseases | EmaxHealth
Epigenetics of neurodegenerative diseases - WikipediaEpigenetics of neurodegenerative diseases - Wikipedia
Estrogen and neurodegenerative diseases - WikipediaEstrogen and neurodegenerative diseases - Wikipedia
Neurodegenerative disease with dementiaNeurodegenerative disease with dementia
Category:Deaths from neurodegenerative disease - WikipediaCategory:Deaths from neurodegenerative disease - Wikipedia
Challenges in neurodegenerative diseasesChallenges in neurodegenerative diseases
Neurodegenerative Disease News, ResearchNeurodegenerative Disease News, Research
Neurodegenerative diseases: Deadly droplets | EurekAlert! Science NewsNeurodegenerative diseases: Deadly droplets | EurekAlert! Science News
Brain enzyme could prevent Alzheimers, neurodegenerative diseaseBrain enzyme could prevent Alzheimer's, neurodegenerative disease
Neurodegenerative Diseases: Mechanisms and TherapiesNeurodegenerative Diseases: Mechanisms and Therapies
Protein Misfolding and Neurodegenerative DiseasesProtein Misfolding and Neurodegenerative Diseases
Breakthroughs in antemortem diagnosis of neurodegenerative diseases | PNASBreakthroughs in antemortem diagnosis of neurodegenerative diseases | PNAS
What kills neurons in neurodegenerative disease?What kills neurons in neurodegenerative disease?
Neurodegenerative DiseasesNeurodegenerative Diseases
Neurodegenerative disease: Restricting eating times may boost life qualityNeurodegenerative disease: Restricting eating times may boost life quality
Environmental Factors in Neurodegenerative Diseases, Volume 1 - 1st EditionEnvironmental Factors in Neurodegenerative Diseases, Volume 1 - 1st Edition
New impetus for treatment neurodegenerative diseases | EurekAlert! Science NewsNew impetus for treatment neurodegenerative diseases | EurekAlert! Science News
Neurodegenerative diseases as proteinopathies-driven immune disorders. - PubMed - NCBINeurodegenerative diseases as proteinopathies-driven immune disorders. - PubMed - NCBI
Scientists Clarify Editing Error Underlying Genetic Neurodegenerative Disease - RedorbitScientists Clarify Editing Error Underlying Genetic Neurodegenerative Disease - Redorbit
Learning faster with neurodegenerative disease - ScienceBlog.comLearning faster with neurodegenerative disease - ScienceBlog.com
Treatment for neurodegenerative diseases - Colton, Carol A.Treatment for neurodegenerative diseases - Colton, Carol A.
JCI - The genetic epidemiology of neurodegenerative diseaseJCI - The genetic epidemiology of neurodegenerative disease
Gene Therapy Prevents Neurodegenerative DiseaseGene Therapy Prevents Neurodegenerative Disease
Understanding Neurodegenerative DiseaseUnderstanding Neurodegenerative Disease
Nutritional therapy could potentially treat childhood neurodegenerative disease | Fox NewsNutritional therapy could potentially treat childhood neurodegenerative disease | Fox News
Causes and Consequences of Oxidative Stress in Neurodegenerative Diseases | SpringerLinkCauses and Consequences of Oxidative Stress in Neurodegenerative Diseases | SpringerLink
Creatine for neuroprotection in neurodegenerative disease: end of story? | SpringerLinkCreatine for neuroprotection in neurodegenerative disease: end of story? | SpringerLink
Fetal gene therapy for neurodegenerative disease of infants. - PubMed - NCBIFetal gene therapy for neurodegenerative disease of infants. - PubMed - NCBI
AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPsychiatry and PsychologyPhenomena and ProcessesDisciplines and OccupationsInformation ScienceHealth CareGeographicals
Neurodegenerative DiseasesNerve DegenerationAmyotrophic Lateral SclerosisNeuronsAlzheimer Diseasetau ProteinsHuntington DiseaseBrainParkinson Diseasealpha-SynucleinNerve Tissue ProteinsTauopathiesNeuroprotective AgentsDisease Models, AnimalInclusion BodiesHeredodegenerative Disorders, Nervous SystemProteostasis DeficienciesMicrogliaPrionsPrion DiseasesMice, TransgenicSynucleinsAmyloid beta-PeptidesSpinocerebellar AtaxiasFrontotemporal Lobar DegenerationCell DeathOxidative StressMutationTrinucleotide Repeat ExpansionFrontotemporal DementiaFriedreich AtaxiaMitochondriaAutophagyNeuronal Ceroid-LipofuscinosesGuamAmyloidAgingDementiaProtein FoldingCells, CulturedNeurofibrillary TanglesLewy Body DiseaseAstrocytesPeptidesNeurotoxinsParkinsonian DisordersSuperoxide DismutaseMice, Inbred C57BLModels, BiologicalLewy BodiesAxonal TransportCentral Nervous SystemTrinucleotide RepeatsMotor Neuron DiseaseSupranuclear Palsy, ProgressiveMitochondrial DiseasesMotor NeuronsUbiquitinCentral Nervous System DiseasesHippocampusCycasIron-Binding ProteinsProteasome Endopeptidase ComplexMuscular Atrophy, SpinalCerebral CortexPick Disease of the BrainSignal TransductionCell SurvivalRNA-Binding Protein FUSNeurogliaGliosisApoptosisGene Expression RegulationNervous System DiseasesPlaque, AmyloidReactive Oxygen SpeciesMultiple System AtrophyNuclear ProteinsAnimals, Genetically ModifiedSubstantia NigraMolecular ChaperonesPrPSc ProteinsImmunohistochemistrybeta-SynucleinRotarod Performance TestAmino Acids, DiaminoParkinson Disease, SecondaryAxonsIntranuclear Inclusion BodiesDNA Repeat ExpansionSpinal CordDopaminergic NeuronsAtrophyBlotting, WesternCorpus StriatumTDP-43 ProteinopathiesAntioxidantsCyclin-Dependent Kinase 5PhenotypeNeurofilament ProteinsAmyloid beta-Protein PrecursorNeuroaxonal DystrophiesAtaxiaCell LineEncephalitisPrPC ProteinsTrauma, Nervous SystemCreutzfeldt-Jakob SyndromeCerebellumMolecular Sequence DataMice, KnockoutGlial Fibrillary Acidic ProteinMachado-Joseph DiseaseLysosomesNitro CompoundsAmyloidogenic ProteinsDopamine1-Methyl-4-phenylpyridiniumProtein BindingNeurogenesisCognition DisordersHormesisBrain DiseasesSpinocerebellar DegenerationsNeurotoxicity SyndromesMagnetic Resonance ImagingScrapieAmino Acid SequenceWallerian Degenerationgamma-Synuclein1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineBrain ChemistryPC12 CellsMutant ProteinsMicrotubule-Associated ProteinsMitochondrial ProteinsProtein TransportOxidopamineInflammationNiemann-Pick Disease, Type CGreen Fluorescent ProteinsRats, Sprague-DawleySerine ProteasesGlutamic AcidInsomnia, Fatal FamilialDrosophilaBrain-Derived Neurotrophic FactorBlood-Brain BarrierPeptide FragmentsPhosphorylationMitochondrial DynamicsSilver StainingRotenoneThiolester HydrolasesAnalysis of VarianceBehavior, AnimalTime FactorsSpastic Paraplegia, HereditaryCytoprotectionProtein MultimerizationRNA, MessengerNeural Stem CellsProteolysisMicroscopy, Electron, TransmissionMotor ActivityPurkinje CellsMPTP PoisoningDisease ProgressionIntroversion (Psychology)Mutation, MissenseGroup III Histone DeacetylasesSynapsesProtein Structure, QuaternaryBiological MarkersOxidation-ReductionDNA-Binding ProteinsProteinsDrosophila melanogasterHEK293 CellsUbiquitin-Protein LigasesMesencephalonNeuritesNeuropsychological TestsQuinolinic AcidCycadophytaCaenorhabditis elegansProtein Structure, TertiaryStem Cell TransplantationGene ExpressionDrosophila ProteinsTyrosine 3-MonooxygenaseOligodendrogliaAphasia, Primary ProgressiveMyoclonic Epilepsies, ProgressiveIronMice, Neurologic MutantsNeuroimmunomodulationEnzyme InhibitorsHSP70 Heat-Shock ProteinsNeuritisTransfection
DisordersAmyotrophicHuntington'sSeveral neurodegenerative diseasesNeuronsTherapeuticParkinson's DiseaseNeurodegenerationDysfunctionTherapeuticsPrevent neurodegenerative diseasesDiagnosis of neurodegenerativeProgressionMultiple sclerosisCerebrospinal fluidPreclinicalCertain neurodegenerativePrevalenceTreatmentBrainTherapiesResearchParkinsonCommonMitochondrial
Disorders10
Amyotrophic1
Huntington's1
Several neurodegenerative diseases1
Neurons1
Therapeutic2
  • The identification of the etiology and additional factors contributing to the onset and progression of these diseases is of great importance in order to develop both preventive and therapeutic intervention. (medscape.com)
  • Collectively, these capabilities are crucial components to improve the scientific understanding of complex neurodegenerative diseases, develop the next generation of therapeutic approaches, and enhance the social care and structures for patients, their families and health care providers. (usc.edu)
Parkinson's Disease10
Neurodegeneration2
  • Other studies have found similar results, including one conducted at the Massachusetts Institute of Technology in 2013, which found reduction of calories can protect against the neurodegeneration linked to a wide range of progressive, age-related brain disease. (upi.com)
  • We hope that these results will add another way to use information about what's happening in different parts of the body to detect the presence of disease before neurodegeneration takes hold, causing irreversible damage. (technologynetworks.com)
Dysfunction1
  • Early diagnosis may refer to the timely correct differentiation of a specific disease entity from other conditions that may mimic it in early stages, or it may refer to the early detection of central nervous system dysfunction, prior to the emergence of clinical symptoms. (biomedcentral.com)
Therapeutics1
Prevent neurodegenerative diseases1
  • This review focuses on compounds from macroalgae that exhibit neuroprotective effects and their potential application to treat and/or prevent neurodegenerative diseases. (salishseaweeds.com)
Diagnosis of neurodegenerative1
  • A new study led by Boston Medical Center researchers indicates a well-known biomarker that serves as a marker for earlier diagnosis of neurodegenerative diseases is now detectable in the eye. (technologynetworks.com)
Progression7
Multiple sclerosis1
  • Multiple Sclerosis (MS) which is a debilitating autoimmune disease affecting the nervous system and is most common in young people. (sanoviv.com)
Cerebrospinal fluid2
Preclinical1
Certain neurodegenerative1
  • That is, a person might have a gene that makes them more susceptible to a certain neurodegenerative disease, but whether, when, and how severely the person is affected depends on what environmental factors he or she is exposed to during life. (nih.gov)
Prevalence2
Treatment3
  • This creates a critical need to improve our understanding of what causes neurodegenerative diseases and develop new approaches for treatment and prevention. (nih.gov)
  • Though researchers and clinicians are learning more and more about the diseases, there is still uncertainty in the diagnosis and treatment of these conditions. (emaxhealth.com)
  • BACE1 finding reverses the formation of amyloid plaques in the mice who have Alzheimer's disease, opening a wide door for finding treatment for humans. (emaxhealth.com)
Brain3
  • Neurodegenerative diseases occur when nerve cells in the brain or peripheral nervous system lose function over time and ultimately die. (nih.gov)
  • Fasting is a challenge to your brain, and we think that your brain reacts by activating adaptive stress responses that help it cope with disease," Mattson said. (upi.com)
  • Currently, Mattson is conducting a study with obese people who are at higher risk for cognitive impairment to see if intermittent fasting -- using the 5:2, which includes limiting caloric intake to 500 calories per day on two nonconsecutive days each week -- can help reduce the risk for brain diseases. (upi.com)
Therapies3
  • To accelerate the discovery of improved therapies for these diseases, we are developing screening kits to find drug molecules that correct the malfunctioning methyltransferase proteins. (sbir.gov)
  • Advances in basic neuroscience make it increasingly likely that disease modifying therapies will be developed but these are likely to have maximal impact if they are introduced early in the course of the illness. (biomedcentral.com)
  • Early disease detection would permit the provision of such therapies to those most likely to benefit from them, at the time that they are most likely to be effective. (biomedcentral.com)
Research4
Parkinson1
  • Fatal, neurodegenerative diseases (NDs) such as Alzheimer's and Parkinson' are dramatically increasingly in our aging society. (cecam.org)
Common1
Mitochondrial1
  • Here, we review how proteomics has been applied to neurodegenerative diseases in order to characterize the relationship existing between protein aggregation and mitochondrial alterations. (medscape.com)
Cutting calories may help prevent neurodegenerative diseases - UPI.com
Cutting calories may help prevent neurodegenerative diseases - UPI.com (upi.com)
Neurodegenerative disease mechanism and potential drug identified | EurekAlert! Science News
Neurodegenerative disease mechanism and potential drug identified | EurekAlert! Science News (eurekalert.org)
Turning off the protein tap -- A new clue to neurodegenerative disease | EurekAlert! Science News
Turning off the protein tap -- A new clue to neurodegenerative disease | EurekAlert! Science News (eurekalert.org)
Specific Transfection of Inflamed Brain by Macrophages: A New Therapeutic Strategy for Neurodegenerative Diseases
Specific Transfection of Inflamed Brain by Macrophages: A New Therapeutic Strategy for Neurodegenerative Diseases (journals.plos.org)
Neurodegenerative diseases Archives - Be Well Buzz
Neurodegenerative diseases Archives - Be Well Buzz (bewellbuzz.com)
Rehabilitative Management of Patients with Parkinson's Disease and other Neurodegenerative Diseases - Education Resources
Rehabilitative Management of Patients with Parkinson's Disease and other Neurodegenerative Diseases - Education Resources (educationresourcesinc.com)
Oxidant/antioxidant properties of Croatian native propolis | Propolis | Scientific Publication | Native Propolis |...
Oxidant/antioxidant properties of Croatian native propolis | Propolis | Scientific Publication | Native Propolis |... (hedera.hr)
Artificial intelligence in neuropathology: deep learning-based assessment of tauopathy | Laboratory Investigation
Artificial intelligence in neuropathology: deep learning-based assessment of tauopathy | Laboratory Investigation (nature.com)
The genetics of prion diseases | Genetics in Medicine
The genetics of prion diseases | Genetics in Medicine (nature.com)
Celery juice: Benefits and myths
Celery juice: Benefits and myths (medicalnewstoday.com)
UCL Queen Square Institute of Neurology - UCL - University College London
UCL Queen Square Institute of Neurology - UCL - University College London (ucl.ac.uk)
Epigenetics of neurodegenerative diseases - Wikipedia
Epigenetics of neurodegenerative diseases - Wikipedia (en.wikipedia.org)
Stop Alzheimer's before it starts : Nature News & Comment
Stop Alzheimer's before it starts : Nature News & Comment (nature.com)
Somatic evolutionary genomics: Mutations during development cause highly variable genetic mosaicism with risk of cancer and...
Somatic evolutionary genomics: Mutations during development cause highly variable genetic mosaicism with risk of cancer and... (pnas.org)
Fragile Brain: Neurodegenerative Diseases - Scientific American
Fragile Brain: Neurodegenerative Diseases - Scientific American (scientificamerican.com)
Book Series: International Review of Neurobiology
Book Series: International Review of Neurobiology (elsevier.com)
Fragile Brain: Neurodegenerative Diseases - Scientific American
Fragile Brain: Neurodegenerative Diseases - Scientific American (scientificamerican.com)
Disease areas | Research groups | Imperial College London
Disease areas | Research groups | Imperial College London (imperial.ac.uk)
Partnership Funding Programs | Alzheimer's Association
Partnership Funding Programs | Alzheimer's Association (alz.org)
North America | Medical College of Wisconsin
North America | Medical College of Wisconsin (mcw.edu)
'Helper cells' can turn toxic in brain injury and...
'Helper cells' can turn toxic in brain injury and... (medicalnewstoday.com)
Deadly combination in neurodegenerative diseases revealed | EurekAlert! Science News
Deadly combination in neurodegenerative diseases revealed | EurekAlert! Science News (eurekalert.org)
Vaccines for Neurodegenerative Diseases | The New York Academy of Sciences
Vaccines for Neurodegenerative Diseases | The New York Academy of Sciences (nyas.org)
The MFN2 V705I Variant Is Not a Disease-Causing Mutation: A Segregation Analysis in a CMT2 Family
The MFN2 V705I Variant Is Not a Disease-Causing Mutation: A Segregation Analysis in a CMT2 Family (hindawi.com)
International research partnerships | Alzheimer's Society
International research partnerships | Alzheimer's Society (alzheimers.org.uk)
University of Leeds | News > Health > Testing new cancer treatment which could banish chemotherapy