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)

Paired helical filaments, a constituent of neurofibrillary tangles in Alzheimer's disease, consist primarily of the microtubule-associated protein tau. However, the process by which the detergent-insoluble filaments of the neurofibrillary tangles are formed from soluble tau remains unknown. Here, we present a potential mechanism for the abnormal aggregation of tau in Alzheimer's disease: the covalent cross-linking of tau by the enzyme transglutaminase. Macromolecular complexes of tau, formed in the presence of transglutaminase, were found to be insoluble in ionic detergent, beta-mercaptoethanol, guanidine-HCl, and urea and, furthermore, demonstrated an increased immunoreactivity with the monoclonal antibody Alz-50. Electron microscopic studies revealed that tau cross-linked by transglutaminase has a defined filamentous structure. These results indicate that transglutaminase, the activity of which has been shown to increase during programmed cell death, may play a role in the formation of pathology associated with Alzheimer's disease.
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PMID:Transglutaminase catalyzes the formation of sodium dodecyl sulfate-insoluble, Alz-50-reactive polymers of tau. 810 81

We have reported that many sites of tau in fetal brain (fetal-tau) as well as in paired helical filaments (PHF-tau) are phosphorylated. In the present study, we used site-specific antibodies and peptide mapping to examine protein phosphatases involved in dephosphorylation of fetal-tau and PHF-tau. Immunoblot analysis and electrophoretic mobility showed that protein phosphatases 1 and 2A and calcineurin could dephosphorylate fetal-tau and PHF-tau. Phosphoserines 199, 202, 396, and 413 and phosphothreonine 231, numbered according to the longest human tau isoform, were dephosphorylated, as shown by the immunoblot analysis. Phosphoserine 422 was dephosphorylated by protein phosphatase 2A and calcineurin, but not by protein phosphatase 1. Peptide mapping with Achromobacter lyticus protease 1 showed that phosphoserines 199, 202, 235, and 396 and phosphothreonine 231 were dephosphorylated by protein phosphatases. Fetal-tau was more rapidly dephosphorylated by protein phosphatase 2A and calcineurin than PHF-tau. Interestingly, PHF-tau which had not been solubilized with guanidine HCl was little dephosphorylated by protein phosphatases. Thus, PHF-tau in neurofibrillary tangles of Alzheimer's disease brain is likely to be resistant to dephosphorylation by protein phosphatases.
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PMID:Dephosphorylation of fetal-tau and paired helical filaments-tau by protein phosphatases 1 and 2A and calcineurin. 872 Jan 39

A new fluorescence formed while microtubule-associated protein tau was incubated at 25 and 37C for hours, with its maximum excitation at 230 and 280 nm, respectively. The fluorescence completely formed after tau was incubated in phosphate buffer and Tris-HCl buffer for approximately 20 h, with a relaxation phase about 2-4 h. The light scattering of the sample solution improved during formation of the fluorescence when tau was incubated. Both the fluorescence and tau oligomers did not form when tau was incubated in the buffers containing DTT. On the other hand, heparin improved both tau aggregation and the fluorescence formation. It suggests that the fluorescence comes from tau polymerization, which may follow the mechanism of tyrosine-tyrosinate emission for a protein not containing any tryptophan residues. This new fluorescence could be used as a probe to tau polymers.
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PMID:The fluorescent characterization of the polymerized microtubule-associated protein Tau. 1092 52

In the brains of Alzheimer's disease patients, the tau protein dissociates from the axonal microtubule and abnormally aggregates to form a paired helical filament (PHF). One of the priorities in Alzheimer research is to clarify the mechanism of PHF formation. Although several reports on the regulation of tau assembly have been published, it is not yet clear whether in vivo PHFs are composed of beta-structures or alpha-helices. Since the four-repeat microtubule-binding domain (4RMBD) of the tau protein has been considered to play an essential role in PHF formation, its heparin-induced assembly propensity was investigated by the thioflavin fluorescence method to clarify what conformation is most preferred for the assembly. We analyzed the assembly propensity of 4RMBD in Tris-HCl buffer with different trifluoroethanol (TFE) contents, because TFE reversibly induces the transition of the random structure to the alpha-helical structure in an aqueous solution. Consequently, it was observed that the 4RMBD assembly is most significantly favored to proceed in the 10-30% TFE solution, the concentration of which corresponds to the activated transition state of 4RMBD from a random structure to an alpha-helical structure, as determined from the circular dichroism (CD) spectral changes. Since such an assembly does not occur in a buffer containing TFE of < 10% or > 40%, the intermediate conformation between the random and alpha-helical structures could be most responsible for the PHF formation of 4RMBD. This is the first report to clarify that the non-native alpha-helical intermediate in transition from random coil is directly associated with filament formation at the start of PHF formation.
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PMID:Conformational transition state is responsible for assembly of microtubule-binding domain of tau protein. 1497 51