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)

Brains obtained within 2-4 hours post mortem and histopathologically confirmed for Alzheimer's disease and non-Alzheimer brains from age-matched controls were examined for in-vitro assembly of microtubules and neurofilaments. Microtubule assembly was observed only in control but not in Alzheimer brains, and neurofilaments were obtained from both types of brain. The microtubule-associated protein tau, which stimulates assembly of microtubules from tubulin, was abnormally phosphorylated in Alzheimer but not in control brain microtubule preparations. Alzheimer brains did not show the presence of any inhibitor of microtubule assembly or any abnormality of tubulin. DEAE-dextran, a polycation which mimics tau in stimulating microtubule assembly, induced the assembly of microtubules in Alzheimer brain. Tubulin from both normal and Alzheimer brains was labelled on western blots by a monoclonal antibody to the tyrosinylated carboxy-terminal epitope of alpha tubulin. These studies suggest that in Alzheimer's disease tubulin can be assembled into brain microtubules, but the process is defective, probably because of abnormal phosphorylation of tau. This post-translational alteration of tau might be the cause of the neurofibrillary abnormality in Alzheimer's disease.
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PMID:Defective brain microtubule assembly in Alzheimer's disease. 287 14

In Alzheimer's disease, paired helical filaments composed mainly of abnormally phosphorylated tau accumulate in certain selected neurons of the brain, and microtubules are rarely seen in the affected cells. In the present study, the binding of 32P-labeled 8-azidoguanosine triphosphate ([gamma-32P]8N3GTP), the photoaffinity analogue of GTP to the beta-subunit of tubulin in brain homogenates was found to be markedly lower in patients with Alzheimer's disease than in aged control human cases. No significant differences were observed in the levels of the alpha- and beta-subunits of tubulin between Alzheimer's disease and control brains obtained 2-7 h postmortem. In nine of 19 Alzheimer's disease and 11 of 12 control autopsied brains (2-7 h postmortem and stored at -75 degrees C) tubulin was isolated successfully from brain cytosol by in vitro polymerization induced with DEAE-dextran. The GTP binding was observed in the two cycled assembled microtubule preparations from all the normal control, and in eight of nine Alzheimer's disease cases. Alzheimer's disease microtubule preparations contained varying amounts of abnormally phosphorylated tau, whereas no abnormal tau was detected in the control brain preparations. Addition of bovine tau to bovine, normal human, and Alzheimer's disease brain tubulin preparations markedly increased GTP binding to the beta-subunit. An alkaline phosphatase-treated paired helical filament-enriched preparation increased by approximately twofold the GTP binding to bovine brain tubulin. GTP binding to tubulin prepared by phosphocellulose chromatography of two cycled microtubules from three Alzheimer's disease and three normal control brains, revealed insignificant differences between the two groups. These findings have suggested that (1) tau protein promotes the GTP binding to the beta-subunit of tubulin, and (2) the breakdown of the microtubule system in brains of patients with Alzheimer's disease might in part be due to the abnormal phosphorylation of tau which depresses the GTP binding.
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PMID:Guanosine triphosphate binding to beta-subunit of tubulin in Alzheimer's disease brain: role of microtubule-associated protein tau. 783 71

The mechanism of dephosphorylation of multiphosphorylated proteins in the brain is not well understood. We have used the multiphosphorylated protein, phosvitin as a model substrate and undertaken the purification and characterization of brain phosphatases that preferentially dephosphorylate multiphosphorylated proteins. Two phosvitin phosphatase activities, termed Phosvitin Phosphatase 1 and 2 (PvP1, PvP2), which show acidic pH optima were resolved from the 33,000g supernatant fraction from rat brain by a procedure employing successive DEAE-cellulose, Sepharose 6B, second DEAE-cellulose and FPLC/Superose 6 chromatography steps. Following FPLC/Superose 6 size exclusion chromatography of PvP1 and PvP2, single peaks of phosvitin phosphatase activities were eluted in the range of 160-220 kDa with acidic pH optima. When FPLC/Sepharose 6 chromatography was performed in the presence of 0.5 M NaCl and 0.1% Triton X-100, low molecular mass protein phosphatase forms were produced in addition to the high-M, activity peak, ranging from 25 to 35 kDa (PvP1) and from 15 to 25 kDa (PvP2). Under these conditions, both high- and low-M, forms of PvP1 and PvP2 exhibited neutral pH optima. Both phosphatases dephosphorylate also (i) phosphorylase a, (ii) the alpha and beta subunits of phosphorylase kinase, and (iii) the microtubule-associated protein tau, phosphorylated by cAMP-dependent protein kinase. The present results suggest that two forms of protein phosphatases, displayed molecular and biochemical characteristics both similar and distinct from type 1 and type 2A protein phosphatases, are present in rat brain.
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PMID:Partial purification and characterization of two phosvitin phosphatases from rat brain. 862 49