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).
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.
Tauopathies
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.
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)
Cyclin-Dependent Kinase 5
Microtubules
Neurofibrils
Microtubule-Associated Proteins
Phosphorylation
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.
Glycogen Synthase Kinase 3
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)
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.
Tubulin
A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from SPERM FLAGELLUM; CILIA; and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to COLCHICINE; VINCRISTINE; and VINBLASTINE.
Neuropil Threads
Abnormal structures located chiefly in distal dendrites and, along with NEUROFIBRILLARY TANGLES and SENILE PLAQUES, constitute the three morphological hallmarks of ALZHEIMER DISEASE. Neuropil threads are made up of straight and paired helical filaments which consist of abnormally phosphorylated microtubule-associated tau proteins. It has been suggested that the threads have a major role in the cognitive impairment seen in Alzheimer disease.
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.
Brain Chemistry
Neurons
Neurodegenerative Diseases
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)
S100 Calcium Binding Protein beta Subunit
Glycogen Synthase Kinases
A class of protein-serine-threonine kinases that was originally found as one of the three types of kinases that phosphorylate GLYCOGEN SYNTHASE. Glycogen synthase kinases along with CA(2+)-CALMODULIN DEPENDENT PROTEIN KINASES and CYCLIC AMP-DEPENDENT PROTEIN KINASES regulate glycogen synthase activity.
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.
Mice, Transgenic
Protein Isoforms
Peptide Fragments
Proline-Directed Protein Kinases
Microscopy, Electron
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
Okadaic Acid
Cattle
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
Amino Acid Sequence
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.
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.
Disease Models, Animal
Proline
Serine
Immunoblotting
Chromosomes, Human, Pair 17
Blotting, Western
Protein Phosphatase 2
A phosphoprotein phosphatase subtype that is comprised of a catalytic subunit and two different regulatory subunits. At least two genes encode isoforms of the protein phosphatase catalytic subunit, while several isoforms of regulatory subunits exist due to the presence of multiple genes and the alternative splicing of their mRNAs. Protein phosphatase 2 acts on a broad variety of cellular proteins and may play a role as a regulator of intracellular signaling processes.
Electrophoresis, Polyacrylamide Gel
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)
Protein Binding
Calcium-Calmodulin-Dependent Protein Kinases
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
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))
Mutation
Deamidation and isoaspartate formation in smeared tau in paired helical filaments. Unusual properties of the microtubule-binding domain of tau. (1/2608)
An extensive loss of a selected population of neurons in Alzheimer's disease is closely related to the formation of paired helical filaments (PHFs). The most striking characteristic of PHFs upon Western blotting is their smearing. According to a previously described protocol (Morishima-Kawashima, M., Hasegawa, M., Takio, K., Suzuki, M., Titani, K., and Ihara, Y. (1993) Neuron 10, 1151-1160), smeared tau was purified, and its peptide map was compared with that of soluble (normal) tau. A CNBr fragment from soluble tau (CN5; residues 251-419 according to the 441-residue isoform) containing the microtubule-binding domain migrated at 15 and 18 kDa on SDS-polyacrylamide gel electrophoresis, whereas that from smeared tau exhibited two larger, unusually broad bands at approximately 30 and approximately 45 kDa, presumably representing dimers and trimers of CN5. In the peptide map of smeared tau-derived CN5, distinct peaks eluting at unusual locations were noted. Amino acid sequence and mass spectrometric analyses revealed that these distinct peptides bear isoaspartate at Asn-381 and Asp-387. Because no unusual peptides other than aspartyl or isoaspartyl peptide were found in the digests of smeared tau-derived CN5, it is likely that site-specific deamidation and isoaspartate formation are involved in its dimerization and trimerization and thus in PHF formation in vivo. (+info)The development of cell processes induced by tau protein requires phosphorylation of serine 262 and 356 in the repeat domain and is inhibited by phosphorylation in the proline-rich domains. (2/2608)
The differentiation of neurons and the outgrowth of neurites depends on microtubule-associated proteins such as tau protein. To study this process, we have used the model of Sf9 cells, which allows efficient transfection with microtubule-associated proteins (via baculovirus vectors) and observation of the resulting neurite-like extensions. We compared the phosphorylation of tau23 (the embryonic form of human tau) with mutants in which critical phosphorylation sites were deleted by mutating Ser or Thr residues into Ala. One can broadly distinguish two types of sites, the KXGS motifs in the repeats (which regulate the affinity of tau to microtubules) and the SP or TP motifs in the domains flanking the repeats (which contain epitopes for antibodies diagnostic of Alzheimer's disease). Here we report that both types of sites can be phosphorylated by endogenous kinases of Sf9 cells, and that the phosphorylation pattern of the transfected tau is very similar to that of neurons, showing that Sf9 cells can be regarded as an approximate model for the neuronal balance between kinases and phosphatases. We show that mutations in the repeat domain and in the flanking domains have opposite effects. Mutations of KXGS motifs in the repeats (Ser262, 324, and 356) strongly inhibit the outgrowth of cell extensions induced by tau, even though this type of phosphorylation accounts for only a minor fraction of the total phosphate. This argues that the temporary detachment of tau from microtubules (by phosphorylation at KXGS motifs) is a necessary condition for establishing cell polarity at a critical point in space or time. Conversely, the phosphorylation at SP or TP motifs represents the majority of phosphate (>80%); mutations in these motifs cause an increase in cell extensions, indicating that this type of phosphorylation retards the differentiation of the cells. (+info)Increased poly(ADP-ribosyl)ation of nuclear proteins in Alzheimer's disease. (3/2608)
Experimental studies indicate that overactivation of the DNA repair protein poly(ADP-ribose) polymerase (PARP) in response to oxidative damage to DNA can cause cell death due to depletion of NAD+. Oxidative damage to DNA and other macromolecules has been reported to be increased in the brains of patients with Alzheimer's disease. In the present study we sought evidence of PARP activation in Alzheimer's disease by immunostaining sections of frontal and temporal lobe from autopsy material of 20 patients and 10 controls, both for PARP itself and for its end-product, poly(ADP-ribose). All of the brains had previously been subjected to detailed neuropathological examination to confirm the diagnosis of Alzheimer's disease or, in the controls, to exclude Alzheimer's disease-type pathology. Double immunolabelling for poly(ADP-ribose) and microtubule-associated protein 2 (MAP2), glial fibrillary-acidic protein (GFAP), CD68, A beta-protein or tau was used to assess the identity of the cells with poly(ADP-ribose) accumulation and their relationship to plaques and neurofibrillary tangles. Both PARP- and poly(ADP-ribose)-immunolabelled cells were detected in a much higher proportion of Alzheimer's disease (20 out of 20) brains than of control brains (5 out of 10) (P = 0.0018). Double-immunolabelling for poly(ADP-ribose) and markers of neuronal, astrocytic and microglial differentiation (MAP2, GFAP and CD68, respectively) showed many of the cells containing poly(ADP-ribose) to be neurons. Most of these were small pyramidal neurons in cortical laminae 3 and 5. A few of the cells containing poly(ADP-ribose) were astrocytes. No poly(ADP-ribose) accumulation was detected in microglia. Double-immunolabelling for poly(ADP-ribose) and tau or A beta-protein indicated that the cells with accumulation of poly(ADP-ribose) did not contain tangles and relatively few occurred within plaques. Our findings indicate that there is enhanced PARP activity in Alzheimer's disease and suggest that pharmacological interventions aimed at inhibiting PARP may have a role in slowing the progression of the disease. (+info)Association of an extended haplotype in the tau gene with progressive supranuclear palsy. (4/2608)
We describe two extended haplotypes that cover the human tau gene. In a total of approximately 200 unrelated caucasian individuals there is complete disequilibrium between polymorphisms which span the gene (which covers approximately 100 kb of DNA). This suggests that the establishment of the two haplotypes was an ancient event and either that recombination is suppressed in this region, or that recombinant genes are selected against. Furthermore, we show that the more common haplotype (H1) is significantly over-represented in patients with progressive supranuclear palsy (PSP), extending earlier reports of an association between an intronic dinucleotide polymorphism and PSP. (+info)Heparin-induced conformational change in microtubule-associated protein Tau as detected by chemical cross-linking and phosphopeptide mapping. (5/2608)
In Alzheimer's disease, microtubule-associated protein tau becomes abnormally phosphorylated and aggregates into paired helical filaments. Sulfated glycosaminoglycans such as heparin and heparan sulfate were shown to accumulate in pretangle neurons, stimulate in vitro tau phosphorylation, and cause tau aggregation into paired helical filament-like filaments. The sulfated glycosaminoglycan-tau interaction was suggested to be the central event in the development of neuropathology in Alzheimer's disease brain (Goedert, M., Jakes, R., Spillantini, M. G., Hasegawa, M., Smith, M. J., and Crowther, R. A. (1996) Nature 383, 550-553). The biochemical mechanism by which sulfated glycosaminoglycans stimulate tau phosphorylation and cause tau aggregation remains unclear. In this study, disuccinimidyl suberate (DSS), a bifunctional chemical cross-linker, cross-linked tau dimers, tetramers, high molecular size aggregates, and two tau species of sizes 72 and 83 kDa in the presence of heparin. In the absence of heparin only dimeric tau was cross-linked by DSS. Fast protein liquid chromatography gel filtration revealed that 72- and 83-kDa species were formed by intramolecular cross-linking of tau by DSS. These observations indicate that heparin, in addition to causing aggregation, also induces a conformational change in tau in which reactive groups are unmasked or move closer leading to the DSS cross-linking of 72- and 83-kDa species. Heparin-induced structural changes in tau molecule depended on time of heparin exposure. Dimerization and tetramerization peaked at 48 h, whereas conformational change was completed within 30 min of heparin exposure. Heparin exposure beyond 48 h caused an abrupt aggregation of tau into high molecular size species. Heparin stimulated tau phosphorylation by neuronal cdc2-like kinase (NCLK) and cAMP-dependent protein kinase. Phosphopeptide mapping and phosphopeptide sequencing revealed that tau is phosphorylated by NCLK on Thr212 and Thr231 and by cAMP-dependent protein kinase on Ser262 only in the presence of heparin. Heparin stimulation of tau phosphorylation by NCLK showed dependence on time of heparin exposure and correlated with the heparin-induced conformational change of tau. Our data suggest that heparin-induced conformational change exposes new sites for phosphorylation within tau molecule. (+info)The expression of casein kinase 2alpha' and phosphatase 2A activity. (6/2608)
Protein phosphatase 2A (PP2A) activity may be differentially regulated by the expression of proteins containing a related amino acid sequence motif such as the casein kinase 2alpha (CK2alpha) subunit or SV40 small t antigen (SVt). Expression of CK2alpha increases PP2A activity whereas SVt decreases its activity. In this work we have tested for the effect of the expression of a third protein containing a similar motif that could be involved in PP2A regulation, the catalytic casein kinase 2alpha' subunit. Our results show that despite the structural similarity of this protein with the other CK2 catalytic (alpha) subunit, the function of the two subunits with respect to the modulation of PP2A activity is quite different: CK2alpha increases whereas CK2alpha' slightly decreases PP2A activity. (+info)Polymerization of tau peptides into fibrillar structures. The effect of FTDP-17 mutations. (7/2608)
The peptides corresponding to the four repeats found in the microtubule binding region of tau protein were synthesized and their ability for self-aggregation in presence of heparin or chondroitin sulfate was measured. Mainly, only the peptide containing the third tau repeat is able to form polymers in a high proportion. Additionally, the peptide containing the second repeat aggregates with a very low efficiency. However, when this peptide contains the mutation (P301L), described in a fronto temporal dementia, it is able to form polymers at a higher extent. Finally, it is suggested to have a role for the first and fourth tau repeats. It could be to decrease the ability of the third tau repeat for self-aggregation in the presence of heparin. (+info)Mutations in tau reduce its microtubule binding properties in intact cells and affect its phosphorylation. (8/2608)
In vitro evidence has suggested a change in the ability of tau bearing mutations associated with fronto-temporal dementia to promote microtubule assembly. We have used a cellular assay to quantitate the effect of both isoform differences and mutations on the physiological function of tau. Whilst all variants of tau bind to microtubules, microtubule extension is reduced in cells transfected with 3-relative to 4-repeat tau. Mutations reduce microtubule extension with the P301L mutation having a greater effect than the V337M mutation. The R406W mutation had a small effect on microtubule extension but, surprisingly, tau with this mutation was less phosphorylated in intact cells than the other variants. (+info) Tauopathies are a group of neurodegenerative disorders characterized by the abnormal phosphorylation and aggregation of the microtubule-associated protein tau. These proteins form insoluble fibrils that accumulate in neurons and other cells, leading to progressive loss of structure and function.
Examples of tauopathies include:
1. Alzheimer's disease: The most common cause of dementia, characterized by the deposition of amyloid-β plaques, neurofibrillary tangles, and synaptic loss.
2. Frontotemporal dementia (FTD): A group of disorders that affect the frontal and temporal lobes of the brain, causing changes in personality, behavior, and language.
3. Progressive supranuclear palsy (PSP): A rare disorder characterized by rapid eye movements, gaze instability, and falls.
4. Corticobasal degeneration (CBD): A rare disorder characterized by asymmetric degeneration of the brain, including the cerebral cortex and basal ganglia.
5. Pick's disease: A rare disorder characterized by the accumulation of tau protein in the brain, leading to progressive cognitive decline and atrophy of certain areas of the brain.
6. Primary lateral sclerosis (PLS): A rare disorder characterized by weakness and wasting of the muscles of the legs and feet, without involvement of the arms.
7. Tauopathy with preserved cognition (TPC): A rare disorder characterized by the accumulation of tau protein in the brain, but without significant cognitive decline.
Tauopathies are often diagnosed based on a combination of clinical symptoms, neuroimaging techniques such as magnetic resonance imaging (MRI) or positron emission tomography (PET), and postmortem examination of brain tissue. There is currently no cure for tauopathies, but research into the molecular mechanisms underlying these disorders may lead to the development of new therapeutic strategies in the future.
Alzheimer's disease is a progressive neurological disorder that affects memory, thinking, and behavior. It is the most common form of dementia, accounting for 60-80% of dementia cases. The exact cause of Alzheimer's disease is not yet fully understood, but it is believed to be caused by a combination of genetic, lifestyle, and environmental factors.
The symptoms of Alzheimer's disease can vary from person to person and may progress slowly over time. Early symptoms may include memory loss, confusion, and difficulty with problem-solving. As the disease progresses, individuals may experience language difficulties, visual hallucinations, and changes in mood and behavior.
There is currently no cure for Alzheimer's disease, but there are several medications and therapies that can help manage its symptoms and slow its progression. These include cholinesterase inhibitors, memantine, and non-pharmacological interventions such as cognitive training and behavioral therapy.
Alzheimer's disease is a significant public health concern, affecting an estimated 5.8 million Americans in 2020. It is the sixth leading cause of death in the United States, and its prevalence is expected to continue to increase as the population ages.
There is ongoing research into the causes and potential treatments for Alzheimer's disease, including studies into the role of inflammation, oxidative stress, and the immune system. Other areas of research include the development of biomarkers for early detection and the use of advanced imaging techniques to monitor progression of the disease.
Overall, Alzheimer's disease is a complex and multifactorial disorder that poses significant challenges for individuals, families, and healthcare systems. However, with ongoing research and advances in medical technology, there is hope for improving diagnosis and treatment options in the future.
Pick disease, also known as frontotemporal dementia (FTD), is a rare neurodegenerative disorder that affects the brain's frontal and temporal lobes. It is characterized by the progressive degeneration of neurons in these regions, leading to changes in personality, behavior, and cognitive function.
There are several types of Pick disease, including:
1. Primary progressive aphasia (PPA): This type of Pick disease is characterized by a gradual decline in language abilities, including speaking, reading, and writing. Individuals with PPA may also experience changes in personality and behavior.
2. Behavioral variant FTD (bvFTD): This type of Pick disease is characterized by changes in personality, behavior, and social conduct, as well as a decline in cognitive function.
3. Progressive supranuclear palsy (PSP): This type of Pick disease is characterized by a combination of Parkinson's disease-like symptoms, such as rigidity and difficulty with movement, as well as dementia.
4. Corticobasal degeneration (CBD): This type of Pick disease is characterized by a combination of frontal and parietal lobe degeneration, leading to changes in personality, behavior, and cognitive function.
Symptoms of Pick disease can vary depending on the type and progression of the disorder. Common symptoms include:
* Changes in personality and behavior
* Decline in cognitive function, including memory loss and difficulty with language
* Difficulty with movement and coordination
* Loss of initiative and interest in activities
* Social withdrawal
* Depression and anxiety
There is no cure for Pick disease, but there are several medications and therapies that can help manage its symptoms. These include:
* Cholinesterase inhibitors: These medications can help improve cognitive function and slow the progression of dementia.
* Memantine: This medication can help with memory loss and cognitive function.
* Physical therapy: This can help with movement and coordination problems.
* Speech therapy: This can help with language and communication difficulties.
* Occupational therapy: This can help with daily living skills and activities.
It's important to note that Pick disease is a rare disorder, and there is limited research on its causes and treatment options. However, with the right medications and therapies, people with Pick disease can improve their quality of life and manage their symptoms effectively.
Nerve degeneration, also known as neurodegeneration, is a process where nerve cells (neurons) are damaged or destroyed, leading to loss of function and often causing symptoms such as pain, weakness, and numbness.
There are many different types of nerve degeneration that can occur in various parts of the body, including:
1. Alzheimer's disease: A progressive neurological disorder that affects memory and cognitive function, leading to degeneration of brain cells.
2. Parkinson's disease: A neurodegenerative disorder that affects movement and balance, caused by the loss of dopamine-producing neurons in the brain.
3. Amyotrophic lateral sclerosis (ALS): A progressive neurological disease that affects nerve cells in the brain and spinal cord, leading to muscle weakness, paralysis, and eventually death.
4. Multiple sclerosis: An autoimmune disease that affects the central nervous system, causing inflammation and damage to nerve fibers.
5. Diabetic neuropathy: A complication of diabetes that can cause damage to nerves in the hands and feet, leading to pain, numbness, and weakness.
6. Guillain-Barré syndrome: An autoimmune disorder that can cause inflammation and damage to nerve fibers, leading to muscle weakness and paralysis.
7. Chronic inflammatory demyelinating polyneuropathy (CIDP): An autoimmune disorder that can cause inflammation and damage to nerve fibers, leading to muscle weakness and numbness.
The causes of nerve degeneration are not always known or fully understood, but some possible causes include:
1. Genetics: Some types of nerve degeneration may be inherited from one's parents.
2. Aging: As we age, our nerve cells can become damaged or degenerate, leading to a decline in cognitive and physical function.
3. Injury or trauma: Physical injury or trauma to the nervous system can cause nerve damage and degeneration.
4. Infections: Certain infections, such as viral or bacterial infections, can cause nerve damage and degeneration.
5. Autoimmune disorders: Conditions such as Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy (CIDP) are caused by the immune system attacking and damaging nerve cells.
6. Toxins: Exposure to certain toxins, such as heavy metals or pesticides, can damage and degenerate nerve cells.
7. Poor nutrition: A diet that is deficient in essential nutrients, such as vitamin B12 or other B vitamins, can lead to nerve damage and degeneration.
8. Alcoholism: Long-term alcohol abuse can cause nerve damage and degeneration due to the toxic effects of alcohol on nerve cells.
9. Drug use: Certain drugs, such as chemotherapy drugs and antiviral medications, can damage and degenerate nerve cells.
10. Aging: As we age, our nerve cells can deteriorate and become less functional, leading to a range of cognitive and motor symptoms.
It's important to note that in some cases, nerve damage and degeneration may be irreversible, but there are often strategies that can help manage symptoms and improve quality of life. If you suspect you have nerve damage or degeneration, it's important to seek medical attention as soon as possible to receive an accurate diagnosis and appropriate treatment.
Neurodegenerative diseases are a group of conditions that affect the brain and spinal cord, leading to progressive loss of neural function and eventually death. These diseases are characterized by the gradual degeneration of neurons, which can result in cognitive decline, motor dysfunction, and a variety of other symptoms.
Some common examples of neurodegenerative diseases include:
1. Alzheimer's disease: A progressive loss of cognitive function, memory, and thinking skills that is the most common form of dementia.
2. Parkinson's disease: A disorder that affects movement, balance, and coordination, causing tremors, rigidity, and difficulty with walking.
3. Huntington's disease: An inherited condition that causes progressive loss of cognitive, motor, and psychiatric functions.
4. Amyotrophic lateral sclerosis (ALS): A disease that affects the nerve cells responsible for controlling voluntary muscle movement, leading to muscle weakness, paralysis, and eventually death.
5. Prion diseases: A group of rare and fatal disorders caused by misfolded proteins in the brain, leading to neurodegeneration and death.
6. Creutzfeldt-Jakob disease: A rare, degenerative, and fatal brain disorder caused by an abnormal form of a protein called a prion.
7. Frontotemporal dementia: A group of diseases that affect the front and temporal lobes of the brain, leading to changes in personality, behavior, and language.
Neurodegenerative diseases can be caused by a variety of factors, including genetics, age, lifestyle, and environmental factors. They are typically diagnosed through a combination of medical history, physical examination, laboratory tests, and imaging studies. Treatment options for neurodegenerative diseases vary depending on the specific condition and its underlying causes, but may include medications, therapy, and lifestyle changes.
Preventing or slowing the progression of neurodegenerative diseases is a major focus of current research, with various potential therapeutic strategies being explored, such as:
1. Stem cell therapies: Using stem cells to replace damaged neurons and restore brain function.
2. Gene therapies: Replacing or editing genes that are linked to neurodegenerative diseases.
3. Small molecule therapies: Developing small molecules that can slow or prevent the progression of neurodegenerative diseases.
4. Immunotherapies: Harnessing the immune system to combat neurodegenerative diseases.
5. Lifestyle interventions: Promoting healthy lifestyle choices, such as regular exercise and a balanced diet, to reduce the risk of developing neurodegenerative diseases.
In conclusion, neurodegenerative diseases are a complex and diverse group of disorders that can have a profound impact on individuals and society. While there is currently no cure for these conditions, research is providing new insights into their causes and potential treatments. By continuing to invest in research and developing innovative therapeutic strategies, we can work towards improving the lives of those affected by neurodegenerative diseases and ultimately finding a cure.
Dementia is a broad term that describes a decline in mental ability severe enough to interfere with daily life. It can affect memory, thinking, language, judgment, and behavior. Dementia can be caused by a variety of underlying diseases, such as Alzheimer's disease, vascular dementia, Lewy body dementia, and frontotemporal dementia.
There are several types of dementia, each with its own set of symptoms and characteristics. Some common types of dementia include:
* Alzheimer's disease: This is the most common form of dementia, accounting for 50-70% of all cases. It is a progressive disease that causes the death of brain cells, leading to memory loss and cognitive decline.
* Vascular dementia: This type of dementia is caused by problems with blood flow to the brain, often as a result of a stroke or small vessel disease. It can cause difficulty with communication, language, and visual-spatial skills.
* Lewy body dementia: This type of dementia is characterized by the presence of abnormal protein deposits called Lewy bodies in the brain. It can cause a range of symptoms, including memory loss, confusion, hallucinations, and difficulty with movement.
* Frontotemporal dementia: This is a group of diseases that affect the front and temporal lobes of the brain, leading to changes in personality, behavior, and language.
The symptoms of dementia can vary depending on the underlying cause, but common symptoms include:
* Memory loss: Difficulty remembering recent events or learning new information.
* Communication and language difficulties: Struggling to find the right words or understand what others are saying.
* Disorientation: Getting lost in familiar places or having difficulty understanding the time and date.
* Difficulty with problem-solving: Trouble with planning, organizing, and decision-making.
* Mood changes: Depression, anxiety, agitation, or aggression.
* Personality changes: Becoming passive, suspicious, or withdrawn.
* Difficulty with movement: Trouble with coordination, balance, or using utensils.
* Hallucinations: Seeing or hearing things that are not there.
* Sleep disturbances: Having trouble falling asleep or staying asleep.
The symptoms of dementia can be subtle at first and may progress slowly over time. In the early stages, they may be barely noticeable, but as the disease progresses, they can become more pronounced and interfere with daily life. It is important to seek medical advice if you or a loved one is experiencing any of these symptoms, as early diagnosis and treatment can help improve outcomes.
Plaques, amyloid are a type of protein aggregate that accumulates in the brain and is associated with various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and prion diseases. Amyloid plaques are composed of abnormally folded protein fibrils that are resistant to degradation and accumulate extracellularly in the brain. These plaques disrupt normal brain function and are thought to contribute to the progression of neurodegenerative diseases.
The term "amyloid" refers specifically to the type of protein aggregate that forms these plaques, and is derived from the Greek word for "flour-like." Amyloidosis is the general term used to describe the condition of having amyloid deposits in the body, while Alzheimer's disease is a specific type of amyloidosis that is characterized by the accumulation of beta-amyloid peptides in the brain.
Plaques, amyloid play a central role in the pathogenesis of many neurodegenerative diseases, and understanding their formation and clearance is an area of ongoing research. In addition to their role in Alzheimer's disease, amyloid plaques have been implicated in other conditions such as cerebral amyloid angiopathy, primary lateral sclerosis, and progressive supranuclear palsy.
Plaques, amyloid are composed of a variety of proteins, including beta-amyloid peptides, tau protein, and apolipoprotein E (apoE). The composition and structure of these plaques can vary depending on the underlying disease, and their presence is often associated with inflammation and oxidative stress.
In addition to their role in neurodegeneration, amyloid plaques have been implicated in other diseases such as type 2 diabetes and cardiovascular disease. The accumulation of amyloid fibrils in these tissues can contribute to the development of insulin resistance and atherosclerosis, respectively.
Overall, plaques, amyloid are a complex and multifaceted area of research, with many open questions remaining about their formation, function, and clinical implications. Ongoing studies in this field may provide valuable insights into the pathogenesis of various diseases and ultimately lead to the development of novel therapeutic strategies for these conditions.
In conclusion, plaques, amyloid are a hallmark of several neurodegenerative diseases, including Alzheimer's disease, and have been associated with inflammation, oxidative stress, and neurodegeneration. The composition and structure of these plaques can vary depending on the underlying disease, and their presence is often linked to the progression of the condition. Furthermore, amyloid plaques have been implicated in other diseases such as type 2 diabetes and cardiovascular disease, highlighting their potential clinical significance beyond neurodegeneration. Ongoing research into the mechanisms of amyloid plaque formation and clearance may lead to the development of novel therapeutic strategies for these conditions.
A disease model, animal is a living organism that has been used to study and understand a specific disease or set of diseases. These models are used by researchers to better comprehend the underlying causes and mechanisms of a particular disease, as well as to develop and test new treatments. Animals can be used as disease models for a variety of reasons:
1) They share similarities with humans: Many animal species share similar biological and physiological characteristics with humans, making them useful for studying human diseases. For example, mice and rats are often used to study diseases such as diabetes, heart disease, and cancer because they have similar metabolic and cardiovascular systems to humans.
2) They can be genetically manipulated: Animal disease models can be genetically engineered to develop specific diseases or to model human genetic disorders. This allows researchers to study the progression of the disease and test potential treatments in a controlled environment.
3) They can be used to test drugs and therapies: Before new drugs or therapies are tested in humans, they are often first tested in animal models of disease. This allows researchers to assess the safety and efficacy of the treatment before moving on to human clinical trials.
4) They can provide insights into disease mechanisms: Studying disease models in animals can provide valuable insights into the underlying mechanisms of a particular disease. This information can then be used to develop new treatments or improve existing ones.
5) Reduces the need for human testing: Using animal disease models reduces the need for human testing, which can be time-consuming, expensive, and ethically challenging. However, it is important to note that animal models are not perfect substitutes for human subjects, and results obtained from animal studies may not always translate to humans.
6) They can be used to study infectious diseases: Animal disease models can be used to study infectious diseases such as HIV, TB, and malaria. These models allow researchers to understand how the disease is transmitted, how it progresses, and how it responds to treatment.
7) They can be used to study complex diseases: Animal disease models can be used to study complex diseases such as cancer, diabetes, and heart disease. These models allow researchers to understand the underlying mechanisms of the disease and test potential treatments.
8) They are cost-effective: Animal disease models are often less expensive than human clinical trials, making them a cost-effective way to conduct research.
9) They can be used to study drug delivery: Animal disease models can be used to study drug delivery and pharmacokinetics, which is important for developing new drugs and drug delivery systems.
10) They can be used to study aging: Animal disease models can be used to study the aging process and age-related diseases such as Alzheimer's and Parkinson's. This allows researchers to understand how aging contributes to disease and develop potential treatments.
Supranuclear Palsy, Progressive (SNP) is a rare brain disorder that affects movement, balance, and eye movements. It is characterized by rapid progression, with worsening symptoms over time, and can lead to severe disability and dementia. SNP is caused by degeneration of certain areas in the brainstem and cerebellum, leading to a decline in movement control and cognitive function.
There are two main types of SNP:
1. Steele-Richardson-Olszewski syndrome (SRO): This is the most common form of SNP and is characterized by progressive gait disturbance, rigidity, and dementia.
2. Richardson's syndrome: This type is characterized by a more rapid progression of symptoms, including early cognitive decline and dementia.
The symptoms of SNP can vary from person to person and may include:
* Difficulty walking or maintaining balance
* Rigidity or stiffness in the muscles
* Loss of coordination and equilibrium
* Slurred speech and difficulty with swallowing
* Vision problems, including double vision or difficulty focusing
* Cognitive decline and dementia
There is currently no cure for SNP, but various medications and therapies can help manage the symptoms and slow down the progression of the disease. These may include:
* Medications to control rigidity and tremors
* Physical therapy to maintain mobility and balance
* Speech therapy to improve communication and swallowing difficulties
* Occupational therapy to assist with daily activities
* Cognitive therapy to slow down cognitive decline
It is important for individuals with SNP to receive timely and accurate diagnosis and treatment from a team of specialists, including neurologists, geriatricians, physical therapists, occupational therapists, speech therapists, and social workers. With appropriate care and support, individuals with SNP can improve their quality of life and maintain independence for as long as possible.
Creutzfeldt-Jakob Syndrome (CJD) is a rare, degenerative, fatal brain disorder caused by an abnormal form of a protein called a prion. It is the most common type of transmissible spongiform encephalopathy (TSE).
Symptoms:
* Rapidly progressive dementia
* Ataxia (loss of coordination and balance)
* Myoclonus (involuntary muscle jerks)
* Visual disturbances
* Cognitive decline
Diagnosis:
* Clinical evaluation
* Neuroimaging studies (MRI, CT scans)
* Electroencephalography (EEG)
* Cerebrospinal fluid (CSF) examination
Treatment and Management:
* There is no cure for CJD, but various medications can be used to manage the symptoms.
* Palliative care is essential to alleviate suffering and improve quality of life.
* Supportive care includes physical therapy, speech therapy, and occupational therapy.
Prognosis:
* CJD is a rapidly progressive disease with a poor prognosis, typically leading to death within 1-2 years after onset of symptoms.
Causes and Risk Factors:
* The cause of CJD is the transmission of misfolded prions, which are infectious proteins that accumulate in the brain.
* The most common form of transmission is through medical procedures using contaminated tissue, such as corneal transplants or dura mater grafts.
* There is also a rare genetic form of CJD, which is inherited from one's parents.
Complications:
* CJD can lead to various complications, including pneumonia, seizures, and coma.
* The disease can also cause psychiatric symptoms such as depression, anxiety, and hallucinations.
In conclusion, Creutzfeldt-Jakob Syndrome is a rare and fatal brain disorder characterized by rapid neurological deterioration, prion accumulation in the brain, and poor prognosis. It is important to be aware of the causes and risk factors of CJD, as well as its symptoms and complications, to provide appropriate diagnosis and treatment for affected individuals.
Tau protein
Wikimedia Commons has media related to Tau proteins. Look up tau protein or tau in Wiktionary, the free dictionary. tau+ ... In humans, the MAPT gene for encoding tau protein is located on chromosome 17q21, containing 16 exons. The major tau protein in ... Hyperphosphorylated tau disassembles microtubules and sequesters normal tau, MAPT 1 (microtubule associated protein tau 1), ... Tau proteins are found more often in neurons than in non-neuronal cells in humans. One of tau's main functions is to modulate ...
Tau-protein kinase
... protein tau kinase, STK31, tau kinase, [tau-protein] kinase, tau-protein kinase I, tau-protein kinase II, tau-tubulin kinase, ... tau-protein] O-phosphotransferase. Other names in common use include ATP:tau-protein O-hosphotransferase, brain protein kinase ... In enzymology, a tau-protein kinase (EC 2.7.11.26) is an enzyme that catalyzes the chemical reaction ATP + tau protein ⇌ {\ ... O-phospho-tau-protein Thus, the two substrates of this enzyme are ATP and tau protein, whereas its two products are ADP and O- ...
Neuroscience of aging
For example, the tau hypothesis to Alzheimer's proposes that tau protein accumulation results in the breakdown neuron ... Goedert, M.; Spillantini, M. G.; Crowther, R. A. (1 July 1991). "Tau proteins and neurofibrillary degeneration". Brain ... Similarly the protein alpha-synuclein is hypothesized to accumulate in Parkinson's and related diseases. Treatments with ... a tale of two proteins". Annals of Neurology. 59 (3): 449-458. doi:10.1002/ana.20819. ISSN 0364-5134. PMID 16489609. S2CID ...
Alzheimer's disease
The tau hypothesis proposes that tau protein abnormalities initiate the disease cascade. In this model, hyperphosphorylated tau ... A protein called tau stabilises the microtubules when phosphorylated, and is therefore called a microtubule-associated protein ... caused by the accumulation of abnormally folded amyloid beta protein into amyloid plaques, and tau protein into neurofibrillary ... Tau proteins are responsible in neuron's internal support and transport system to carry nutrients and other essential materials ...
David G. Drubin
While isolating the gene encoding microtubule-associated tau protein, a major player in Alzheimer's disease, Drubin developed ... Drubin studied mutants of over 60 proteins, identifying a pathway in budding yeast in which proteins are recruited to endocytic ... Tau protein function in living cells. Journal of Cell Biology, 103(6), 2739-2746. Drubin, D. G., & Nelson, W. J. (1996). ... "Tau protein function in living cells". The Journal of Cell Biology. 103 (6): 2739-2746. doi:10.1083/jcb.103.6.2739. PMC 2114585 ...
GSK-3
Ketamine Tau-protein kinase PDB: 1J1B; Aoki M, Yokota T, Sugiura I, Sasaki C, Hasegawa T, Okumura C, et al. (March 2004). " ... GSK-3 is thought to directly promote Aβ production and to be tied to the process of the hyperphosphorylation of tau proteins, ... "Structural insight into nucleotide recognition in tau-protein kinase I/glycogen synthase kinase 3 beta". Acta Crystallographica ... while the phosphorylation of Beta-catenin by GSK-3 is mediated by the binding of both proteins to Axin, a scaffold protein, ...
Visual selective attention in dementia
Tangles are threads of another protein, tau. Tau twist into abnormal tangles inside brain cells, resulting in failure of the ... Plaques are clumps of a protein called beta-amyloid. They may damage and destroy brain cells by interfering with cell-to-cell ... requiring the normal structure and functioning of tau. It has been suggested that attentional decline in mild AD is perhaps ...
SPTB
Carlier MF, Simon C, Cassoly R, Pradel LA (April 1984). "Interaction between microtubule-associated protein tau and spectrin". ... Wolfe LC, John KM, Falcone JC, Byrne AM, Lux SE (November 1982). "A genetic defect in the binding of protein 4.1 to spectrin in ... Spectrin beta chain, erythrocyte is a protein that in humans is encoded by the SPTB gene. GRCh38: Ensembl release 89: ... "Defining of the minimal domain of protein 4.1 involved in spectrin-actin binding". The Journal of Biological Chemistry. 270 (36 ...
Sleep disorder
The first is an accumulation of beta-amyloid waste forming aggregate "plaques". The second is an accumulation of tau protein. ... As individuals awaken, the production of beta-amyloid protein will be more consistent than its production during sleep. This is ... and there is no protein degradation by the glymphatic clearance. During sleep, the burden is reduced as there is less metabolic ... thus resulting in greater secretion of beta-amyloid protein. The second is that oxidative stress will also increase, which ...
Superficial siderosis
Kondziella D, Zetterberg H (October 2008). "Hyperphosphorylation of tau protein in superficial CNS siderosis". Journal of the ... and elevated levels of the proteins Tau, amyloid beta (Aβ42), neurofilament light chain (NFL), and glial fibrillary acidic ... Ferritin, an iron storage protein, is over-produced in response to excess heme by glial cells in order to sequester iron, with ... Once they eventually break down, they release the heme containing protein hemoglobin. Hemoglobin breaks down and releases iron- ...
Asparagine endopeptidase
AEP cleaves tau protein and amyloid precursor protein. In patients with PD, alpha synuclein is cut by AEP into toxic chunks. ... In AD the plaques are composed of amyloid beta, intracellular neurofibrillary tangles and tau protein. The dysfunction of APP ... AEP is involved in presenting of foreign and self proteins using MHCII protein complex. The role of AEP in immunity is not ... It digests SET protein, which is an inhibitor of DNase, leading to DNA damage and causing damage of the brain. Increased ...
Julie C. Price
PET imaging of tau protein targets: a methodology perspective. Brain Imaging Behav. doi: 10.1007/s11682-018-9847-7[Epub]. PMID ... C, Lois; I, Gonzalez; Ka, Johnson; Jc, Price (April 2019). "PET Imaging of Tau Protein Targets: A Methodology Perspective". ... Price's work then extended to PET imaging of tau burden in AD, with neurofibrillary tangles of hyperphosphorylated tau being ... protein expression, neurotransmitter system function, and tau and amyloid beta plaque burden. Price attended the University of ...
Protein phosphorylation
Tau protein belongs to a group of Microtubule Associated Proteins (MAPs) which, among several things, help stabilize ... There is an adequate amount that the tau protein needs to be phosphorylated to function, but hyperphosphorylation of tau ... Protein phosphorylation is a reversible post-translational modification of proteins. In eukaryotes, protein phosphorylation ... protein A phosphorylates protein B, and B phosphorylates C. However, in another signaling pathway, protein D phosphorylates A, ...
USP9Y
Mesco ER, Timiras PS (1992). "Tau-ubiquitin protein conjugates in a human cell line". Mech. Ageing Dev. 61 (1): 1-9. doi: ... which cleave the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins. Mutations in this gene have ...
YWHAZ
Tau protein, and VIM. 14-3-3 protein GRCh38: Ensembl release 89: ENSG00000164924 - Ensembl, May 2017 GRCm38: Ensembl release 89 ... 14-3-3 protein zeta/delta (14-3-3ζ) is a protein that in humans is encoded by the YWHAZ gene on chromosome 8. The protein ... though it can also bind phosphothreonine proteins and unphosphorylated proteins. By extension, 14-3-3 proteins are involved in ... Hashiguchi M, Sobue K, Paudel HK (August 2000). "14-3-3zeta is an effector of tau protein phosphorylation". The Journal of ...
LY3372689
Its result is to reduce formation of tau protein tangles. A molecule containing radioactive fluorine was used with a PET scan ...
Jennifer L. Ross
"Differential regulation of dynein and kinesin motor proteins by tau". Science. 319 (5866): 1086-1089. Bibcode:2008Sci... ... she developed single-molecule imaging to investigate microtubule motor proteins. These proteins are responsible for the ... Ross images these proteins using a super-resolution microscope and fluorescent tagging. She also created an interdisciplinary ... She is interested in the physical laws the determine the organization of proteins and organelles inside cells. To study the ...
Erika Holzbaur
"Differential regulation of dynein and kinesin motor proteins by tau". Science. 319 (5866): 1086-1089. Bibcode:2008Sci... ... Holzbaur studies various motor proteins, including dyneins, myosins and kinesins. In the axons of neurons, these motor proteins ... She recognized that the cytoplasmic dynein-associated proteins closely resembled a Drosophila gene called Glued, which was ... "Huntingtin-associated Protein 1 (HAP1) Interacts with the p150Glued Bubunit of Dynactin". Human Molecular Genetics. 6 (13): ...
NPEPPS
... as a novel modifier of TAU-induced neurodegeneration with neuroprotective effects via direct proteolysis of TAU protein. The ... "Degradation of tau protein by puromycin-sensitive aminopeptidase in vitro". Biochemistry. 45 (50): 15111-9. doi:10.1021/ ... "Involvement of puromycin-sensitive aminopeptidase in proteolysis of tau protein in cultured cells, and attenuated proteolysis ... The protein has been localized to both the cytoplasm and to cellular membranes. This enzyme degrades enkephalins in the brain, ...
Multiple system atrophy
Tau proteins have been found in some glial cytoplasmic inclusion bodies. Clinical diagnostic criteria were defined in 1998 and ... A modified form of the alpha-synuclein protein within affected neurons may cause MSA. About 55% of MSA cases occur in men, with ... In 2020, researchers at The University of Texas Health Science Center at Houston concluded that protein misfolding cyclic ... June 2011). "Copy number loss of (src homology 2 domain containing)-transforming protein 2 (SHC2) gene: discordant loss in ...
Di-deuterated linoleic acid ethyl ester
PSP is a disease involving modification and dysfunction of tau protein; RT001's mechanism of action both lowers lipid ...
Dephosphorylation
This is due to the dysfunction of dephosphorylation mechanisms at specific amino acids on the tau protein. Tau ... The microtubule-associated protein tau is abnormally hyperphosphorylated when isolated from the brain of patients who suffer ... Deficiency or modification of one or both proteins may be involved in abnormal phosphorylation of tau in Alzheimer's disease ... The dephosphorylation of proteins is a mechanism for modifying behavior of a protein, often by activating or inactivating an ...
Don W. Cleveland
Cleveland, Don W. (1977). Purification and properties of tau, a microtubule associated protein which induces assembly of ... Mandelkow, E.-M.; Mandelkow, E. (March 20, 2012). "Biochemistry and Cell Biology of Tau Protein in Neurofibrillary Degeneration ... Cleveland's doctoral dissertation was titled "Purification and properties of tau, a microtubule associated protein which ... showing it to have characteristics of a natively unfolded protein. Tau is now recognized to accumulate in Alzheimer's disease ...
Retrotope
PSP is a disease involving modification and dysfunction of tau protein; RT001's mechanism of action both lowers lipid ...
Protein kinase N1
"Phosphorylation of microtubule-associated protein tau by stress-activated protein kinases". FEBS Lett. 409 (1): 57-62. doi: ... Serine/threonine-protein kinase N1 is an enzyme that in humans is encoded by the PKN1 gene. The protein encoded by this gene ... "Sequential phosphorylation of Tau by glycogen synthase kinase-3beta and protein kinase A at Thr212 and Ser214 generates the ... "Analysis of RhoA-binding proteins reveals an interaction domain conserved in heterotrimeric G protein beta subunits and the ...
Reinforced lipids
PSP is a disease involving modification and dysfunction of tau protein; RT001's mechanism of action both lowers lipid ...
Biochemistry of Alzheimer's disease
AD is also considered a tauopathy due to abnormal aggregation of the tau protein, a microtubule-associated protein expressed in ... AD is also considered a tauopathy due to abnormal aggregation of the tau protein, a microtubule-associated protein expressed in ... Therein, it is suggested that "Tau-ists" believe that the tau protein abnormalities initiate the disease cascade, while "ba- ... Support for the tau hypothesis also derives from the existence of other diseases known as tauopathies in which the same protein ...
Tauopathy
When tau becomes hyperphosphorylated, the protein dissociates from the microtubules in axons. Then, tau becomes misfolded and ... Tangles are formed by hyperphosphorylation of the microtubule protein known as tau, causing the protein to dissociate from ... Alzheimer 'tau' protein far surpasses amyloid in predicting toll on brain tissue Dickson DW (August 2009). "Neuropathology of ... Tauopathy belongs to a class of neurodegenerative diseases involving the aggregation of tau protein into neurofibrillary or ...
Apoptosis-antagonizing transcription factor
"Rb binding protein Che-1 interacts with Tau in cerebellar granule neurons. Modulation during neuronal apoptosis". Molecular and ... Protein AATF is a protein that in humans is encoded by the AATF gene. The protein encoded by this gene was identified on the ... "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. Bibcode:2005Natur. ... AATF+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH) AATF human gene location in the UCSC ...
Gerard Schellenberg
"A novel Alzheimer disease locus located near the gene encoding tau protein". Molecular Psychiatry. 21 (1): 108-117. doi:10.1038 ... "Tau is a candidate gene for chromosome 17 frontotemporal dementia". Annals of Neurology. 43 (6): 815-825. doi:10.1002/ana. ... the MAPT mutations which cause FTLD-tau type, and subsequently the MAPT association with Guam amyotrophic lateral sclerosis/ ...
Peptide bond
Peptides and proteins are chains of amino acids held together by peptide bonds (and sometimes by a few isopeptide bonds). ... tau \sim 20} seconds at room temperature). The transition states ω = ± 90 ∘ {\displaystyle \omega =\pm 90^{\circ }} requires ... Conformational protein folding is usually much faster (typically 10-100 ms) than cis-trans isomerization (10-100 s). A ... In the unfolded state of proteins, the peptide groups are free to isomerize and adopt both isomers; however, in the folded ...
Learning to rank
Kendall's tau; Spearman's rho. DCG and its normalized variant NDCG are usually preferred in academic research when multiple ... In computational biology for ranking candidate 3-D structures in protein structure prediction problem. In recommender systems ...
Complementarity plot
... is a graphical tool for structural validation of atomic models for both folded globular proteins and protein-protein interfaces ... Touw, W.G., and Vriend, G., On the complexity of Engh and Huber refinement restraints: the angle tau as example. Acta Cryst D, ... CPdock was primarily developed as a scoring function to serve as an initial filter in protein-protein docking and can be a very ... A version of the plot (CPint) has also been built and made available to probe similar errors in protein-protein interfaces. In ...
Galectin-9
The protein has N- and C- terminal carbohydrate-binding domains connected by a link peptide. Multiple alternatively spliced ... proteopathic aggregates such as tau fibrils and amyloids, and signaling pathways inducing lysosomal permeabilization such as ... However, it can also interact with other proteins (CLEC7A, CD137, CD40). For example, an interaction with CD40 on T-cells ... Galectin-9 was first isolated from mouse embryonic kidney in 1997 as a 36 kDa beta-galactoside lectin protein. Human galectin-9 ...
Heart-type fatty acid binding protein
"Serum heart-type fatty acid-binding protein and cerebrospinal fluid tau: marker candidates for dementia with Lewy bodies". ... Heart-type fatty acid binding protein (hFABP) also known as mammary-derived growth inhibitor is a protein that in humans is ... Heart-type Fatty Acid-Binding Protein (H-FABP) is a small cytoplasmic protein (15 kDa) released from cardiac myocytes following ... "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957-68. doi:10.1016/j.cell ...
John Q. Trojanowski
... especially the role of abnormal protein aggregates (misfolded proteins) in these diseases. The major goal of his research was ... tau in Alzheimer's disease, alpha-synuclein in Parkinson's disease, and TDP-43 in Amyotrophic Lateral Sclerosis (ALS) and ... He and his partner, Virginia Man-Yee Lee, MBA, Ph.D., are noted for identifying the roles of three proteins in ...
Dementia with Lewy bodies
Autopsy studies and amyloid imaging studies using Pittsburgh compound B (PiB) indicate that tau protein pathology and amyloid ... Also, DLB is a synucleinopathy, meaning that it is characterized by abnormal deposits of alpha-synuclein protein in the brain. ... When these clumps of protein form, neurons function less optimally and eventually die. Neuronal loss in DLB leads to profound ... The exact cause is unknown but involves formation of abnormal clumps of protein in neurons throughout the brain. Manifesting as ...
Glucocorticoid receptor
... the heat shock protein 70 (hsp70) and the protein FKBP4 (FK506-binding protein 4). The endogenous glucocorticoid hormone ... "Role of important hydrophobic amino acids in the interaction between the glucocorticoid receptor tau 1-core activation domain ... Hulkko SM, Wakui H, Zilliacus J (August 2000). "The pro-apoptotic protein death-associated protein 3 (DAP3) interacts with the ... resides in the cytosol complexed with a variety of proteins including heat shock protein 90 (hsp90), ...
John Hardy (geneticist)
... splice-site mutations in tau with the inherited dementia FTDP-17". Nature. 393 (6686): 702-705. Bibcode:1998Natur.393..702H. ... "Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease". Nature. 349 (6311 ...
Microtubule
This first class comprises MAPs with a molecular weight below 55-62 kDa, and are called τ (tau) proteins. In-vitro, tau ... MAP-1 proteins consists of a set of three different proteins: A, B and C. The C protein plays an important role in the ... including the motor proteins dynein and kinesin, microtubule-severing proteins like katanin, and other proteins important for ... Additionally, tau proteins have also been shown to stabilize microtubules in axons and have been implicated in Alzheimer's ...
Enhancer of polycomb homolog 2 (drosophila)
... is a protein that in humans is encoded by the EPC2 gene. GRCh38: Ensembl release 89 ... t-tau, and p-tau181p in the ADNI cohort". Neurology. 76 (1): 69-79. doi:10.1212/WNL.0b013e318204a397. PMC 3030225. PMID ... May 2008). "A genome-wide association study identifies protein quantitative trait loci (pQTLs)". PLOS Genetics. 4 (5): e1000072 ... "ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation ...
Human alphaherpesvirus 1
... scientists showed that treating infected cells with antiviral agents decreased the accumulation of β-amyloid and tau protein, ...
Hilal Lashuel
Tau and several N-terminal fragments of the Huntingtin protein. In addition, in collaboration with Ashraf Brik, the Lashuel ... He then obtained a PhD jointly from the Texas A&M University and the Scripps Research Institute in 2000, working on protein ... In 2019, ND biosciences received the Michael J. Fox Foundation for Parkinson's Research (MJFF) grant for its Protein Science ... paving the way for deciphering the post-translational modification code of these proteins in health and disease. The role of ...
Yafa Yarkoni
TAU+discovery%3A+Excess+protein+linked+to+Alzheimer%27s+must+be+prevented+before+it+accumulates+on+brain.+After+its+ ... "TAU discovery: Excess protein linked to Alzheimer's must be prevented before it accumulates on brain": "The latest Israeli ...
Annonaceae
The disorder is a so-called tauopathy associated with a pathologic accumulation of tau protein in the brain. Experimental ...
Electric dipole moment
... tau }}} are given by U = − p ⋅ E , τ = p × E , {\displaystyle U=-\mathbf {p} \cdot \mathbf {E} ,\qquad \ {\boldsymbol {\tau ... Dipole moments can be found in common molecules such as water and also in biomolecules such as proteins. By means of the total ... Ojeda, P.; Garcia, M. (2010). "Electric Field-Driven Disruption of a Native beta-Sheet Protein Conformation and Generation of a ...
Tara Spires-Jones
Preventing the spread of tau proteins may enable new synapse connections to be formed. Her research has also shown how alpha- ... research has shown that the amyloid beta and tau proteins that cause neuropathological lesions in Alzheimer's disease, ... synuclein protein builds up in neurons that connect cells in Dementia with Lewy Bodies, suggesting that these connections ... contribute to synapse loss and that reducing the level of these proteins prevents synaptic degeneration. ...
Histamine N-methyltransferase
In the mammalian brain, the neurotransmitter activity of histamine is controlled by N(tau)-methylation as diamine oxidase is ... Multiple alternatively spliced transcript variants that encode different proteins have been found for this gene. This article ... In mammals, histamine is metabolized by two major pathways: N(tau)-methylation via histamine N-methyltransferase and oxidative ...
Hartmuth C. Kolb
... for detecting the tau protein in Alzheimer's disease) and with the clinical testing of these tracers, a key highlight being [ ... Kolb's lab has developed a blood plasma assay for phospho-217-Tau (p217Tau), which shows potential as a highly accurate ... most notably the Tau PET tracer [18F]-T807 (aka AV1451, Flortaucipir, Tauvid), now FDA approved for PET imaging of the brain to ... a novel tau positron emission tomography imaging agent for Alzheimer's disease". Alzheimer's & Dementia. 9 (6): 666-676. doi: ...
Supersymmetric theory of stochastic dynamics
... tau (\chi ^{i}(\tau )\delta /\delta x^{i}(\tau )+B_{i}(\tau )\delta /\delta {\bar {\chi }}_{i}(\tau ))A(\Phi )} . In the BRST ... Crumpling paper, protein folding, and many other nonlinear dynamical processes in response to quenches, i.e., to external ( ... tau )-{\mathcal {F}}(x(\tau )))}{\delta x(\tau ')}}} is the Jacobian of the corresponding functional derivative, and the path ... tau }\delta ({\dot {x}}(\tau )-{\mathcal {F}}(x(\tau )))\right)Dx\right\rangle _{\text{noise}},} where F {\displaystyle {\ ...
Frontotemporal lobar degeneration
Mutations in the Tau gene (known as MAPT or Microtubule Associated Protein Tau) can cause a FTLD presenting with tau pathology ... Common proteinopathies that are found in FTLD include the accumulation of tau proteins and TAR DNA-binding protein 43 (TDP-43 ... FTLD-tau is characterised by tau positive inclusion bodies often referred to as Pick-bodies. Examples of FTLD-tau include; ... 1989). "Cloning and sequencing of the cDNA encoding an isoform of microtubule-associated protein tau containing four tandem ...
Chromosome 6
... encoding protein Tripartite motif containing 38 TTBK1: encoding protein Tau tubulin kinase 1 UBR2: ubiquitin protein ligase E3 ... encoding protein Absent in melanoma 1 protein (6q21) AIG1: encoding protein Androgen-induced protein 1 (6q24.2) AKIRIN2: akirin ... tight junction associated protein 1 (6p21.1) TP53COR1 encoding protein Tumor protein p53 pathway corepressor 1 (non-protein ... encoding protein zinc finger with KRAB and SCAN domains 4 ZNF76: zinc finger protein 76 (6p21.31) ZNF193: zinc finger protein ...
CSTF2T
Cleavage stimulation factor 64 kDa subunit, tau variant is a protein that in humans is encoded by the CSTF2T gene. GRCh38: ... 2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. ... 2001). "Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs ... 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. Bibcode: ...
Multiscale modeling
... tau } is given as a linear function of the gradient ∇ u {\displaystyle \nabla u} . Such a choice for τ {\displaystyle \tau } ... USA Multiscale Modeling Tools for Protein Structure Prediction and Protein Folding Simulations, Warsaw, Poland Multiscale ... Important problems include multiscale modeling of fluids, solids, polymers, proteins, nucleic acids as well as various physical ... tau ,\\\nabla \cdot \mathbf {u} =0.\end{array}}} In a wide-variety of applications, the stress tensor τ {\displaystyle \ ...
Charles DeLisi
"BU Theta tau brochure" (PDF). www.thetatauarchives.org. Retrieved 2020-07-25. "Research Brochures , College of Engineering". ... Weng, Zhiping (1997). Protein-ligand binding: Effective free energy calculations (PhD thesis). Boston University. OCLC 38760266 ... genomics and protein and nucleic acid structure and function. Recent activities include mathematical finance and climate change ... where he and his collaborators established one of the earliest protein and DNA sequence databases fully integrated with machine ...
Songi Han
This allows for the mapping of surface water differences around globular proteins. In collaboration with the National High ... 6 July 2017). "RNA stores tau reversibly in complex coacervates". PLOS Biology. 15 (7): e2002183. doi:10.1371/JOURNAL.PBIO. ...
Circadian rhythm
This protein model was developed based on the oscillations of the PER and TIM proteins in the Drosophila. It is based on its ... The period of the rhythm in constant conditions is called the free-running period and is denoted by the Greek letter τ (tau). ... But their proteins levels remain low until dusk, because during daylight also activates the doubletime (dbt) gene. DBT protein ... which facilitate protein-protein interactions; and several photoreceptors that fine-tune the clock to different light ...
Frontiers | Role of Tau as a Microtubule-Associated Protein: Structural and Functional Aspects
Tau is a stabilizing MT associated protein, whose functions are mainly regulated by phosphorylation. A disruption of the MT ... Tau is a stabilizing MT associated protein, whose functions are mainly regulated by phosphorylation. A disruption of the MT ... Since destabilization of MTs after dissociation of Tau could contribute to toxicity in neurodegenerative diseases, a molecular ... Since destabilization of MTs after dissociation of Tau could contribute to toxicity in neurodegenerative diseases, a molecular ...
A structure-based model for the electrostatic interaction of the N-terminus of protein tau with the fibril core of Alzheimer's...
A structure-based model for the electrostatic interaction of the N-terminus of protein tau with the fibril core of Alzheimers ... A structure-based model for the electrostatic interaction of the N-terminus of protein tau with the fibril core of Alzheimers ... A structure-based model for the electrostatic interaction of the N-terminus of protein tau with the fibril core of Alzheimers ... A structure-based model for the electrostatic interaction of the N-terminus of protein tau with the fibril core of Alzheimers ...
RNA binding protein networks in tau pathogenesis | NIH
Expression and purification of tau protein and its frontotemporal dementia variants using a cleavable histidine tag - WRAP:...
Expression and purification of tau protein and its frontotemporal dementia variants using a cleavable histidine tag. Protein ... Recombinant tau protein is widely used to study the biochemical, cellular and pathological aspects of tauopathies, including ... Expression and purification of tau protein and its frontotemporal dementia variants using a cleavable histidine tag ... However, the preparation of recombinant tau is complicated by the proteins propensity to aggregate and form truncation ...
Researchers Create CRISPR 'On-Off Switch' to Control Inherited Genetic Problems Without Changing DNA
Alzheimers and the Tau protein. They selected one gene to use as an example of how CRISPRoff might be applied to therapeutics: ... "What we showed is that this is a viable strategy for silencing Tau and preventing that protein from being expressed," says ... the gene that codes for Tau protein, which is implicated in Alzheimers disease. After testing the method in neurons, they ... for Biomedical Research and have already used the tool in the lab to mostly deactivate the gene that makes the protein Tau, ...
Alzheimer Disease in Down Syndrome: Overview, Pathophysiology/Risk Factors, Epidemiology
Abeta42, total tau protein, and tau phosphorylated at position threonine 181 (P-tau) levels in CSF have sensitivity and ... mainly composed of tau protein, which is encoded by the microtubule-associated protein tau gene [MAPT]), extracellular neuritic ... twisted filamentous proteins composed mainly of hyperphosphorylated tau proteins. [181] This might indicate that changes in tau ... Tau protein. Genes in chromosome 21 regulate this intracellular protein found in the neurofibrillary tangles (NFT). The ...
A physically-modified saline suppresses neuronal apoptosis, attenuates tau phosphorylation and protects memory in an animal...
Neuritic plaques are mainly composed of aggregates of amyloid-β (Aβ) protein while neurofibrillary tangles … ... protein while neurofibrillary tangles are composed of the hyperphosphorylated tau protein. Despite intense investigations, no ... Here, we have undertaken a novel approach to attenuate apoptosis and tau phosphorylation in cultured neuronal cells and in a ... Furthermore, RNS60 also decreased Aβ(1-42)-induced tau phosphorylation via (PI-3 kinase-Akt)-mediated inhibition of GSK-3β. ...
Nutrients | Free Full-Text | Towards an Integrative Understanding of tRNA Aminoacylation-Diet-Host-Gut Microbiome Interactions...
Some proteins marking neurodegenerative pathology, such as tau lack tryptophan. TrpRS exists in cytoplasmic (WARS) and ... TrpRS inhibition by tryptamine and its metabolites preventing tryptophan incorporation into proteins lead to protein ... Tryptophan, a least amino acid in food and proteins that cannot be synthesized by humans competes with frequent amino acids for ... The diminished tryptophan-dependent protein biosynthesis in AD patients is a proof of our model-based disease concept. ...
Yeast biopanning against site-specific phosphorylations in tau. | Protein Eng Des Sel;362023 01 21. | MEDLINE
The detection of site-specific phosphorylation in the microtubule-associated protein tau is emerging as a means to diagnose and ... Yeast biopanning against site-specific phosphorylations in tau. Yeast biopanning against site-specific phosphorylations in tau ... Using yeast cells displaying a previously validated phospho-tau (p-tau) single-chain variable region fragment (scFv), we show ... Proteínas tau/genética; Proteínas tau/química; Anticorpos Monoclonais; Anticorpos de Cadeia Única/genética; Anticorpos de ...
There's a Difference Between Learning a Stranger's Face in Person and On a Screen | Inside Science
3D Model of the Heart's 'Brain' | Inside Science
Genome-wide association study of dietary intake in the UK biobank study and its associations with schizophrenia and other...
A novel Alzheimer disease locus located near the gene encoding tau protein. Mol. Psychiatry 21, 108-117 (2016). ... fat and protein with the fibroblast growth factor 21 (FGF21) gene and associations of consumption of protein intake with the ... Fat mass and the obesity-associated protein (FTO) gene (p = 4.4 × 10−17), one of the most extensively studied genes in the ... Significant genetic correlations between protein intake and BMI (rg = 0.23) have been reported, but no significant evidence for ...
Amyloid Hypothesis For Alzheimer's In Doubt After Lilly's Drug Failure : Shots - Health News : NPR
The failure of an experimental drug that targets clumps of protein inside the brains of Alzheimers patients called into ... One such road might be to target the tau protein, which also accumulates in tangles inside the Alzheimers-hindered brain. ... Fluorescent deconvolution micrograph of cultured glial cells expressing tau protein (in red). Glial cells are nervous system ... Fluorescent deconvolution micrograph of cultured glial cells expressing tau protein (in red). Glial cells are nervous system ...
MAPT gene: MedlinePlus Genetics
The MAPT gene provides instructions for making a protein called tau. Learn about this gene and related health conditions. ... However, abnormal tau is also found in people without MAPT gene mutations. The defective tau protein assembles into abnormal ... The MAPT gene provides instructions for making a protein called tau. This protein is found throughout the nervous system, ... of the tau protein are produced in the adult brain. The isoforms vary in length from 352 to 441 protein building blocks (amino ...
Late NFL WR Vincent Jackson diagnosed with Stage 2 CTE - ESPN
Changing Minds through Neuroscience Inspired fashion | Biological Sciences | University of Southampton
Neurofibrillary tangles are made up of a protein called tau. Normally tau protein is found in the longest part of a brain cell ... We found that, as predicted by the tau and tangle hypothesis, abnormal tau proteins are indeed not able to do their job ... This effectively prevented all of the bad effects of the abnormal tau protein and made the flies well again (Quraishe et al ... In Alzheimers disease the tau protein is abnormal, and many scientists believe that in this state, it cannot do its job ...
SCOP 1.63: Domain ds015 : s015
Family a.118.7.1: 14-3-3 protein [48446] (2 proteins). *Protein tau isoform [48447] (1 species) *Species Human (Homo sapiens) [ ... Class a: All alpha proteins [46456] (171 folds). *. Fold a.118: alpha-alpha superhelix [48370] (17 superfamilies). multihelical ... SCOP: Structural Classification of Proteins and ASTRAL. Release 1.63 (June 2003) Copyright © 1994-2009 The SCOP and Astral ...
Katherine Tucker | UMass Center for Digital Health | Research | UMass Lowell
Gao, L., Tucker, K.L., Andreadis, A. (2005). Transcriptional regulation of the mouse microtubule-associated protein tau. ... Protein and Bone in the Framingham Osteoporosis Study (2005), Grant - NIH/Harvard Medical School. Tucker, K.L. (Co-Investigator ... Brown, A.F., Prado, C.M., Ghosh, S., Leonard, S.M., Arciero, P.J., Tucker, K.L., Ormsbee, M.J. (2019). Higher-protein intake ... Hannan, M.T., Tucker, K.L., Dawson-Hughes, B., Cupples, L.A., Felson, D.T., Kiel, D.P. (2000). Effect of dietary protein on ...
Experimental Drug Shows Promise For Reversing Alzheimer's Disease Symp - ProHealth.com
And in brain neurons of both animal models, the drug significantly reduced levels of tau protein and protein clumps compared ... enabling CMA to get rid of tau and other defective proteins so they cant form those toxic protein clumps." (Also this month, ... "We know that CMA is capable of digesting defective tau and other proteins," said Dr. Cuervo. "But the sheer amount of defective ... Mice with AD who received CA had improved memory, depression, anxiety, walking ability, and reduced tau protein clumps. ...
Silibinin Ameliorates Formaldehyde-Induced Cognitive Impairment by Inhibiting Oxidative Stress
Silibinin inhibits the expression of GSK-3,i,β,/i, in model mice, thereby reducing the phosphorylation of TAU proteins ser396 ... In addition, as one of the pathological changes of AD, TAU protein is also hyperphosphorylated in FA model mice. ... promoted the nuclear transfer of NRF2 and increased the expression of HO-1 but did not significantly increase the protein ... "Tau phosphorylation at serine 396 and serine 404 by human recombinant tau protein kinase II inhibits taus ability to promote ...
Lucy Hicks, Author at Scienceline
Alzheimer Disease, Spinal Cord Injury, and Back Pain Updates
Xia Lab - University of Rochester Medical Center
Nuclear Inhibitor of Protein Phosphatase 1 (NIPP1) Regulates CNS Tau Phosphorylation and Myelination During Development.; ... Protein phosphatase-1 inhibitor-2 promotes PP1γ positive regulation of synaptic transmission.; Frontiers in synaptic ... We are not only interested in short term modifications in the synaptic protein composition through calcium mediated signaling ... pathway, but also CREB mediated gene transcription which provides new proteins for long term modification of the synapse. ...
Breggin.com | Breggin.com - Refounding America - Rediscovering Ourselves
Tau is one of two proteins strongly implicated in the neurodegenerative effects associated with Alzheimers disease. ... A significantly higher percentage of patients in the TAU-only group relapsed at the end of the trial vs the CBT plus TAU group ... patients receiving CBT plus TAU had a 25% greater reduction in the PANSS total score compared with the TAU-only group (47.5% vs ... Patients were randomized to either 10 sessions of individual CBT (intervention group) adjunctive to treatment as usual (TAU) or ...
Microdissected Pyramidal Cell Proteomics of Alzheimer Brain Reveals Alterations in Creatine Kinase B-Type, 14-3-3-γ, and Heat...
2009). Phosphorylation of tau at Ser214 mediates its interaction with 14-3-3 protein: implications for the mechanism of tau ... 2019). Tau binding protein CAPON induces tau aggregation and neurodegeneration. Nat. Commun. 10:2394. ... Protein abundance ratios and SDs were calculated for all proteins containing at least one unique peptide. This was performed by ... 2003). 14-3-3 connects glycogen synthase kinase-3β to tau within a brain microtubule-associated tau phosphorylation complex. J ...
Do blood tests really help diagnose Alzheimer's disease? - Harvard Health
... based on the amyloid-beta protein. It is quite accurate, compared with positron emission tomography (PET) brain scans, which ... PET scans can show that there are excessive amounts of two proteins in the brain: amyloid-beta and tau. These two proteins are ... Several other blood tests, including for tau protein, also are under development. ... Amyloid-beta and tau also can be measured in spinal fluid, and this can be helpful in making the diagnosis. This requires the ...
Preventing Chronic Disease: April 2006: 05 0167
... dementia and mutation of the gene that produces tau protein have been associated with FTD (64). ... As its name implies, Lewy body dementia (LBD) is characterized by the presence of Lewy bodies, proteins in the cerebral cortex ... Recent research has suggested that the CSF of patients with AD has altered levels of proteins associated with neuron ... Decreased B-amyloid 1-42 and increased tau levels in cerebrospinal fluid of patients with Alzheimer disease. JAMA 2003;289:2094 ...
Honolulu: The Missing Link? Tau Mediates Aβ Toxicity at Synapse | ALZFORUM
... on protein tau into dendritic processes, which inevitably could or even must result in phosphorylation of tau at Y18 (Lee et al ... We used an AAV-tau.255 vector to express the same truncated version of tau, which, in contrast to full-length tau.4R and tau. ... Both tau deletion and transgenic tau independently improved the memory of APP23 mice to wild-type levels. Both tau double- ... is why the protein tau remains labeled by some of the most ardent tauists as an axonal protein, c.q. specific axonal marker? ...
A Study of CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease -...
... total tau protein and phosphorylated tau protein levels ... Change in CSF Levels of Total Tau and Phosphorylated Tau [ Time ... Change in CSF levels of total tau and phosphorylated tau [ Time Frame: Baseline to Months 24 and 60 ]. To demonstrate the ... Change in Neurofibrillary Tangle Burden as Measured by Standardized Uptake Ratio (SUVR) of PET Scans With Tau Radiotracer ( ...
Alzheimers Diagnostic Test Market by Procedure, Application& End-users- Global Industry Insights, Trends, Outlook, and...
PhosphorylationNeuronsAlzheimer's DiseaseAmyloid precursNeurofibrillary tanglesMicrotubulesClumpsAmino acidsIsoformsMutationsAbnormal tauAggregatesAccumulationOligomericExtracellularAxonal transportSynapticBiomarkersAccumulateGeneNeurodegenerative diseasesToxicNeuronalParkinson'sMainly expressedReceptorsKinasePathologicalProtein'sFunctionalAdultInhibitorTherapeuticPathwayIntenseSpikeSynapseCellularStructuralResearchersEnzymeBehaviorCellsPresenceExpressionMechanismLevelsFoundDiseasePatientsEarlySpecific
Phosphorylation9
- Tau is a stabilizing MT associated protein, whose functions are mainly regulated by phosphorylation. (frontiersin.org)
- The detection of site-specific phosphorylation in the microtubule-associated protein tau is emerging as a means to diagnose and monitor the progression of Alzheimer's Disease and other neurodegenerative diseases . (bvsalud.org)
- Using yeast cells displaying a previously validated phospho-tau (p-tau) single-chain variable region fragment (scFv), we show selective yeast cell binding based on single amino acid phosphorylation on the antigen . (bvsalud.org)
- Here, we have undertaken a novel approach to attenuate apoptosis and tau phosphorylation in cultured neuronal cells and in a transgenic animal model of AD. (nih.gov)
- Furthermore, RNS60 also decreased Aβ(1-42)-induced tau phosphorylation via (PI-3 kinase-Akt)-mediated inhibition of GSK-3β. (nih.gov)
- Similarly, RNS60 treatment suppressed neuronal apoptosis, attenuated Tau phosphorylation, inhibited glial activation, and reduced the burden of Aβ in the hippocampus and protected memory and learning in 5XFAD transgenic mouse model of AD. (nih.gov)
- Silibinin inhibits the expression of GSK-3 β in model mice, thereby reducing the phosphorylation of TAU proteins ser396 and ser404 mediated by GSK3 β . (hindawi.com)
- Nuclear Inhibitor of Protein Phosphatase 1 (NIPP1) Regulates CNS Tau Phosphorylation and Myelination During Development. (rochester.edu)
- Chlorpyrifos potentiated PKA-dependent phosphorylation of the striatal protein DARPP-32 and the GluR1 subunit of AMPA receptors in mouse brain slices. (cdc.gov)
Neurons9
- In addition, mislocalized Tau in neurons of Tau-overexpressing transgenic mouse brain and of human AD brain directly interacts with the nucleoporins of the nuclear pore complex. (frontiersin.org)
- The discovery that tau may spread by crossing between neurons through synaptic connections is remarkable - tau may be undergoing trans-synaptic spread. (plcontracts.com)
- This protein is found throughout the nervous system, including in nerve cells (neurons) in the brain. (medlineplus.gov)
- In ways that are not fully understood, the MAPT gene mutations responsible for FTDP-17 lead to an accumulation of abnormal tau in neurons and other brain cells. (medlineplus.gov)
- The defective tau protein assembles into abnormal clumps within neurons and other brain cells, although it is unclear what effect these clumps have on cell function and survival. (medlineplus.gov)
- Ever since Dr. George G. Glenner's 1984 discovery that amyloid is the main component of the plaques that riddle the Alzheimer's-afflicted brain, it has been assumed that the protein somehow contributes to the disorder - that it jams up cellular machinery, rendering neurons unable to effectively communicate, to form new memories, to remember where the keys are. (npr.org)
- So she and her colleagues studied a mouse model of early Alzheimer's in which brain neurons were made to produce defective copies of the protein tau. (prohealth.com)
- But if you add neurodegenerative disease to the mix, the effect on the normal protein makeup of brain neurons can be devastating. (prohealth.com)
- Microtubule-associated proteins that are mainly expressed in neurons. (bvsalud.org)
Alzheimer's Disease12
- A disruption of the MT network, which might be caused by Tau loss of function, is observed in a group of related diseases called tauopathies, which includes Alzheimer's disease (AD). (frontiersin.org)
- Recombinant tau protein is widely used to study the biochemical, cellular and pathological aspects of tauopathies, including Alzheimer's disease and frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTPD-17). (warwick.ac.uk)
- A new study investigating Alzheimer's disease reveals that a particular type of harmful protein, known as "oligomeric tau," may play a key role in the development of the disease. (plcontracts.com)
- Alzheimer's disease (AD) is a condition that occurs when harmful proteins called tau build up and spread throughout the brain, leading to the loss of connections between nerve cells, called synapses. (plcontracts.com)
- In Alzheimer's disease, large clusters of the tau protein, known as tangles, accumulate in brain cells, and this is a prominent characteristic of the disease. (plcontracts.com)
- The team identified that within the synapses of individuals who had died from Alzheimer's disease, they observed small clusters of the tau protein known as tau oligomers. (plcontracts.com)
- The researchers from the University of California, San Francisco, and MIT's non-profit Whitehead Institute for Biomedical Research and have already used the tool in the lab to mostly deactivate the gene that makes the protein Tau, which has been implicated in Alzheimer's disease. (goodnewsnetwork.org)
- Would Disrupting the Way Tau Proteins Copy Themselves Slow Alzheimer's Disease? (insidescience.org)
- Studies on brains of people who have died of Alzheimer's disease have shown us that the symptoms of dementia probably arise as a result of the presence of abnormal proteins in brain regions that control memory. (southampton.ac.uk)
- In Alzheimer's disease the tau protein is abnormal, and many scientists believe that in this state, it cannot do its job properly. (southampton.ac.uk)
- Using a fruit fly model of Alzheimer's Disease in which the fruit flies make large quantities of abnormal tau proteins (similar to the ones found in Alzheimer's Disease brains) in their nerve cells, we were able to understand how the abnormal tau proteins affected these nerve cells. (southampton.ac.uk)
- An experimental drug reversed symptoms of Alzheimer's disease (AD) in mice by restarting a cellular cleaning process called chaperone-mediated autophagy (CMA) that removes damaged or unwanted proteins. (prohealth.com)
Amyloid precurs2
- All recognized mutations for AD are associated with increased deposition of amyloid-beta (Abeta), a peptide fragment comprising 39-43 amino acids that derive from the catabolism of the amyloid precursor protein (APP) molecule. (medscape.com)
- 2014). One such element is the amyloid β-peptide (Aβ), which is generated physiologically by proteolytic cleavage of the amyloid precursor protein (APP) by the enzymes β- and γ-secretase (De-Paula et al. (proquest.com)
Neurofibrillary tangles4
- Neuritic plaques are mainly composed of aggregates of amyloid-β (Aβ) protein while neurofibrillary tangles are composed of the hyperphosphorylated tau protein. (nih.gov)
- Neurofibrillary tangles are made up of a protein called tau. (southampton.ac.uk)
- Evidence indicates that abnormal copies of tau clump together to form neurofibrillary tangles that contribute to Alzheimer's. (prohealth.com)
- 2012). Together with neurofibrillary tangles (NFT) composed of hyperphosphorylated Tau protein, plaques composed of fibrillar Aβ is the major neuropathological hallmark of AD (Mott and Hulette, 2005). (proquest.com)
Microtubules3
- A region of the protein called the microtubule-binding domain, which is the part of the protein that attaches (binds) to microtubules, also varies among the isoforms. (medlineplus.gov)
- Normally tau protein is found in the longest part of a brain cell called an axon, where it binds to other proteins called microtubules and forms the cell skeleton (cytoskeleton). (southampton.ac.uk)
- 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. (bvsalud.org)
Clumps4
- These clumps of defective tau build up over time, although it is unclear what effect they have on cell function and survival. (medlineplus.gov)
- This enabled CMA to remove toxic tau protein clumps. (prohealth.com)
- Mice with AD who received CA had improved memory, depression, anxiety, walking ability, and reduced tau protein clumps. (prohealth.com)
- CMA becomes less efficient as people age, increasing the risk that unwanted proteins will accumulate into insoluble clumps that damage cells. (prohealth.com)
Amino acids2
- The isoforms vary in length from 352 to 441 protein building blocks (amino acids). (medlineplus.gov)
- Some of these mutations change single amino acids in the tau protein, most often in the microtubule-binding region. (medlineplus.gov)
Isoforms2
- Six different versions (isoforms) of the tau protein are produced in the adult brain. (medlineplus.gov)
- The resulting imbalance of tau isoforms in the brain interferes with the normal functions of brain cells. (medlineplus.gov)
Mutations5
- Other MAPT gene mutations change the way the gene's instructions are used to build the tau protein. (medlineplus.gov)
- Most of these mutations increase the production of tau with four repeated segments compared to the production of tau with three repeated segments. (medlineplus.gov)
- However, abnormal tau is also found in people without MAPT gene mutations. (medlineplus.gov)
- The MAPT gene mutations responsible for these disorders lead to a buildup of abnormal tau in brain cells. (medlineplus.gov)
- Risdiplam is an mRNA-splicing modifier of survival of motor neuron 2 (SMN2) designed to treat mutations in band 5q that lead to SMN protein deficiency. (medscape.com)
Abnormal tau6
- We found that, as predicted by the tau and tangle hypothesis, abnormal tau proteins are indeed not able to do their job properly. (southampton.ac.uk)
- These results demonstrated, for the first time, that abnormal tau proteins make nerve cells "sick" by disrupting the transport of valuable materials within the nerve cell. (southampton.ac.uk)
- The fly larvae making abnormal tau protein can no longer crawl and navigate as well as normal larvae. (southampton.ac.uk)
- Adult flies making abnormal tau protein are unable to climb effectively and they also die much earlier than normal flies. (southampton.ac.uk)
- We have used this fruit fly model to gain a better understanding of how the cytoskeleton breaks down as a result of abnormal tau being present. (southampton.ac.uk)
- This effectively prevented all of the 'bad' effects of the abnormal tau protein and made the flies 'well' again (Quraishe et al. (southampton.ac.uk)
Aggregates3
- While another protein called amyloid β is also found in the brains of individuals with Alzheimer's, research suggests that the tau protein aggregates are mainly responsible for the development of the disease. (plcontracts.com)
- In fact, Alzheimer's and all other neurodegenerative diseases are characterized by the presence of toxic protein aggregates in patients' brains. (prohealth.com)
- Normally soluble proteins had shifted to being insoluble and at risk for clumping into toxic aggregates. (prohealth.com)
Accumulation3
- The findings suggest that early accumulation of oligomeric tau in nerve connections could be a precursor to Alzheimer's, indicating that reducing these proteins may offer a promising treatment pathway. (plcontracts.com)
- It is marked by widespread accumulation of a protein called tau. (espn.com)
- The accumulation of free radicals in the body can cause oxidative damage to biological macromolecules, such as proteins and lipid membrane. (hindawi.com)
Oligomeric5
- An advantage of the described method is that it enables high yield production of functional oligomeric and monomeric tau, both of which can be used to study the biochemical, physiological and toxic properties of the protein. (warwick.ac.uk)
- High-resolution microscopy was used to discover the presence of oligomeric tau in nerve cell connections in the brains of people with Alzheimer's, including areas previously not associated with tau buildup. (plcontracts.com)
- The researchers found that a specific form of tau, called "oligomeric tau," was present in both the sending and receiving parts of the nerve cell connections, even in areas where there isn't usually a lot of tau buildup. (plcontracts.com)
- Additionally, there was a higher proportion of this oligomeric tau compared to other forms of tau in these nerve cell connections. (plcontracts.com)
- The new study findings suggest that the buildup of oligomeric tau in synaptic connections could be an early indicator of Alzheimer's. (plcontracts.com)
Extracellular2
- Here, we show that antibodies against α-synuclein specifically target and aid in clearance of extracellular α-synuclein proteins by microglia, thereby preventing their actions on neighboring cells. (jneurosci.org)
- MEK 1/2 proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway. (medscape.com)
Axonal transport1
- These pathologically modified Tau molecules perturb MT function and axonal transport, contributing to neurodegeneration. (frontiersin.org)
Synaptic2
- We are not only interested in short term modifications in the synaptic protein composition through calcium mediated signaling pathway, but also CREB mediated gene transcription which provides new proteins for long term modification of the synapse. (rochester.edu)
- Protein phosphatase-1 inhibitor-2 promotes PP1γ positive regulation of synaptic transmission. (rochester.edu)
Biomarkers3
- Jennifer Bramen, PhD, senior research scientist at the Pacific Neuroscience Institute in Santa Monica, CA, not involved in the study, explained to MNT that amyloid and tau are the primary molecular biomarkers in Alzheimer's. (plcontracts.com)
- Several proteins identified in the latter study have been investigated as biomarkers and pathological mediators in AD (Hashimoto M. et al. (proquest.com)
- Compared to 60 controls, brain injury biomarkers (total-Tau, GFAP, NfL, UCH-L1) were increased in acute sera, significantly more so for NfL and UCH-L1, in participants with altered consciousness. (bvsalud.org)
Accumulate1
- The tau oligomers are in addition to the misfolded and phosphorylated tau species that we know accumulate in the [Alzheimer's] affected brain in a progressive fashion over time. (plcontracts.com)
Gene2
- The MAPT gene provides instructions for making a protein called tau. (medlineplus.gov)
- The underlying cause of DMD is a mutation or error in the gene for dystrophin, an essential protein involved in muscle fiber function. (medscape.com)
Neurodegenerative diseases1
- Since destabilization of MTs after dissociation of Tau could contribute to toxicity in neurodegenerative diseases, a molecular understanding of this interaction and its regulation is essential. (frontiersin.org)
Toxic2
- Pure tau in high yield is a requirement for in vitro evaluation of the protein's physiological and toxic functions. (warwick.ac.uk)
- Stopping the spread of toxic tau is a promising strategy to stop the disease in its tracks. (plcontracts.com)
Neuronal1
- An exciting project led by Dr Amrit Mudher (Lecturer in Neuroscience) , aims to investigate the cellular and molecular mechanisms by which the abnormal proteins implicated in neurodegenerative conditions such as AD disturb neuronal function. (southampton.ac.uk)
Parkinson's1
- A structural component of brain cells, tau has also been linked to Alzheimer's and Parkinson's diseases. (medlineplus.gov)
Mainly expressed1
- 14-3-3-γ belongs to a highly conserved protein family mainly expressed in the brain where it regulates diverse functions by binding to kinases, signaling proteins, hydroxylases, and about 170 other ligands (Umahara et al. (proquest.com)
Receptors1
- The novel drug, called CA, increases the amount of receptors that chaperone proteins can bind in order to perform autophagy. (prohealth.com)
Kinase1
- Diisopropyl fluorophosphate and pyrodostigmine bromide, alone or in combination, also increased the aberrant activity of the protein kinase, Cdk5, as indicated by conversion of its activating cofactor p35 to p25. (cdc.gov)
Pathological2
- These abnormal proteins lead to the formation of pathological hallmarks of disease. (southampton.ac.uk)
- In addition, as one of the pathological changes of AD, TAU protein is also hyperphosphorylated in FA model mice. (hindawi.com)
Protein's1
- However, the preparation of recombinant tau is complicated by the protein's propensity to aggregate and form truncation products, necessitating the use of multiple, time-consuming purification methods. (warwick.ac.uk)
Functional3
- They are key structural and functional elements in axons, supporting neurite differentiation and growth, as well as transporting motor proteins along the axons, which use MTs as support tracks. (frontiersin.org)
- This emphasizes the need to understand the finer details of structural and functional aspects of Tau/MTs interaction. (frontiersin.org)
- There are significant structural features in the viral genomic RNA that could, by themselves, explain the retention of the ORF10 nucleotide sequences without the need for a functional protein product. (bvsalud.org)
Adult1
- Dr. David A. Merrill, PhD, adult and geriatric psychiatrist at Providence Saint John's Health Center in Santa Monica, CA, also not involved in the current research, told Medical News Today that the use of advanced microscopy of autopsy samples is "the first to show elevated levels of small tau oligomers in synapses of Alzheimer's patients. (plcontracts.com)
Inhibitor1
- Selumetinib is an inhibitor of mitogen-activated protein kinases 1 and 2 (MEK1/2). (medscape.com)
Therapeutic1
- However, in the last several years, there has been an increase in studies aimed at the therapeutic targeting of Tau. (frontiersin.org)
Pathway1
- We examined the effect of silibinin on the NRF2 signaling pathway, and silibinin promoted the nuclear transfer of NRF2 and increased the expression of HO-1 but did not significantly increase the protein expression of NRF2 in the hippocampus. (hindawi.com)
Intense1
- A sequence from a novel FcaPV type was amplified from a basal cell carcinoma that contained unusual histological evidence of PV infection and intense p16CDKN2A protein (p16) immunostaining. (bvsalud.org)
Spike2
- To explore this question further we made two recombinant viruses, firstly a control virus (WT) based on the genome sequence of the original Wuhan isolate and with the inclusion of the early D614G mutation in the Spike protein. (bvsalud.org)
- Casirivimab-imdevimab is a cocktail made up of two non-competing, neutralizing human immunoglobulin G1 antibodies that target the receptor binding domain of the severe acute respiratory syndrome coronavirus 2 spike protein and block viral entry into human cells. (who.int)
Synapse2
- During the study, researchers utilized advanced microscopy techniques to examine over one million synapses from 42 individuals, allowing the researchers to visualize the proteins within each individual synapse. (plcontracts.com)
- These tangles of tau oligomers were detected in both ends of the synapse, present in the brain cell that transmits signals as well as the brain cell that receives signals. (plcontracts.com)
Cellular1
- The drug works by reinvigorating a cellular cleaning mechanism that gets rid of unwanted proteins by digesting and recycling them. (prohealth.com)
Structural1
- SCOP: Structural Classification of Proteins and ASTRAL. (berkeley.edu)
Researchers1
- In a new study published in Neuron , researchers used a special form of high-resolution microscopy to look at tau proteins in specific regions of the brain in people with Alzheimer's and in those who did not have the condition. (plcontracts.com)
Enzyme2
- But rather than splicing DNA, this enzyme acts on the epigenome, which consists of proteins and small molecules that latch onto DNA and control when and where genes are switched on or off. (goodnewsnetwork.org)
- A different type of investigational medication, so-called BACE inhibitors, prevent amyloid formation in the first place, by neutralizing an enzyme that cuts away amyloid from a larger protein. (npr.org)
Behavior1
- Together with other destabilizing MAPs, such as stathmin, Tau plays a central role in MT dynamics by regulating assembly, dynamic behavior and the spatial organization of MTs. (frontiersin.org)
Cells1
- In addition, the absence of CMA profoundly disrupted proteostasis--the cells' ability to regulate the proteins they contain. (prohealth.com)
Presence1
- These patients were identified by the presence of amyloid or tau protein in PET measurements. (medscape.com)
Expression2
- In this study, we investigated parameters that influence the expression of wild type and FTPD-17 pathogenic tau, in an attempt to identify ways to maximise expression yield. (warwick.ac.uk)
- Here, we report on the influence of the choice of host strain, induction temperature, duration of induction, and media supplementation with glucose on tau expression in Escherichia coli. (warwick.ac.uk)
Mechanism1
- However, the exact mechanism of assembly and stabilization of MTs by Tau remains challenging to characterize due to the inherent dynamics of the system and the disordered nature of Tau. (frontiersin.org)
Levels1
- A recent NIH study found that athletes who needed longer recovery times had slightly higher levels of tau protein released into their blood. (medlineplus.gov)
Found1
- Tau is found hyperphosphorylated in AD, which might account for its loss of MT stabilizing capacity. (frontiersin.org)
Disease1
- Although both Aβ and Tau evidently have major roles in AD, the fact remains that AD is a multifactorial disease and its complexity maybe due to additional, unknown key players. (proquest.com)
Patients1
- Tau protein in cerebrospinal fluid from semantic dementia patients. (cdc.gov)
Early1
- The PV was designated FcaPV7 and contained putative coding regions that were predicted to produce five early proteins and two late ones. (bvsalud.org)
Specific1
- Yeast biopanning against site-specific phosphorylations in tau. (bvsalud.org)
