Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein tau, a major microtubule-binding protein in the brain, comprises six isoforms generated through alternative mRNA splicing. A dysfunctional form of mutant and normal tau is associated or implicated in the pathogenesis of several neurodegenerative disorders. The neuropathological hallmark of these tau-opathies are intraneuronal depositions of fibrillary aggregates of which neurofibrillary tangles are most common. Several distinct transgene mouse models confirmed that tau protein can cause neurodegeneration directly. This study was aimed at identifying proteins that might play a role in the cellular disturbances caused by overexpression of the longest isoform of human tau in the brain of transgenic mice. We found 34 proteins which differed in integrated intensity by a factor of at least 1.5. These proteins could be sorted into several categories. Some of the phenotypic characteristics found in the htau transgenic mice could be related to proteins found in this study. Several proteins are linked to processes involving apoptosis and neuronal death and have been discussed in papers describing neurodegenerative disorders.
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PMID:Proteomics analysis of the neurodegeneration in the brain of tau transgenic mice. 1211 45

Tauopathies are a class of neurodegenerative disorders characterized by neuronal and/or glial inclusions composed of the microtubule-binding protein, tau. Several lines of evidence suggest tau aggregation is central to the neurodegenerative process in tauopathies. First, recent animal and cell model studies find abnormally-modified tau alone may be transmitted between adjacent neurons and spread to anatomically connected brain regions to recapitulate human disease. Further, staging efforts in human autopsy cases suggest a sequential distribution of tau aggregation in the central nervous system that could reflect this observed cell-to-cell transmission of pathogenic tau species in animal models. Finally, pathogenic mutations in the MAPT gene encoding tau protein cause hereditary forms of tauopathy. Clinically, tauopathies can present with a range of phenotypes that include both movement- and cognitive/behavioral-disorders (i.e. frontotemporal dementia spectrum disorders) or non-specific amnestic symptoms in advanced age. A major limitation is that current clinical diagnostic criteria for these disorders do not reliably differentiate underlying tauopathy from other neurodegenerative diseases, such as TDP-43 proteinopathies. Thus, current research efforts are focused on improving the ante mortem diagnosis of tauopathies, including pre-clinical stages of disease, as many therapeutic strategies for emerging disease-modifying therapies focus on preventing abnormal folding and spread of tau pathology.
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PMID:Tauopathies as clinicopathological entities. 2638 41

Introduction: Hyperphosphorylated and aggregated tau protein is the main hallmark of a class of neurodegenerative disorders known as tauopathies. Tau is a microtubule-binding protein which is important for microtubule assembly and stabilization, for proper axonal transport and overall neuronal integrity. However, in tauopathies, tau undergoes aberrant post-translational modifications that fundamentally affect its normal function. The etiology of these devastating diseases is unclear and there is no treatment for these disorders.Areas covered: This review examines the neurobiology of tau, tau post-translational modifications, and tau pathophysiology. Progress regarding the effort to identify and assess novel tau-targeted therapeutic strategies in preclinical studies is also discussed. We performed a search on PubMed of the relevant literature published between 1995 and 2020.Expert opinion: Tau diversity and the lack of clinically available test to diagnose and identify tauopathies are major obstacles; they represent a possible reason for the lack of success of clinical trials. However, given the encouraging advances in PET tau imaging and tau neurobiology, we believe that a more personalized approach could be on the horizon and that this will be key to addressing the heterogeneity of tau pathology.
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PMID:Alzheimer's disease: phenotypic approaches using disease models and the targeting of tau protein. 3211 63

Neurodegenerative disorders are a family of incurable conditions. Among them, Alzheimer's disease and tauopathies are the most common. Pathological features of these two disorders are synaptic loss, neuronal cell death and increased DNA damage. A key pathological protein for the onset and progression of the conditions is the protein tau, a microtubule-binding protein highly expressed in neurons and encoded by the MAPT (microtubule-associated protein tau) gene. Tau is predominantly a cytosolic protein that interacts with numerous other proteins and molecules. Recent findings, however, have highlighted new and unexpected roles for tau in the nucleus of neuronal cells. This review summarizes the functions of tau in the metabolism of DNA, describing them in the context of the disorders.
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PMID:Tau and DNA Damage in Neurodegeneration. 3329 75