Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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

This study determined the prevalence and the prognostic value of the expression of microtubule components in tumors of 19 patients with non small cell lung cancer receiving taxane-based regimens. Patient samples were stained with antibodies directed against total beta tubulin, classes I, II and III beta tubulin isotypes, delta2 alpha tubulin, tau protein, and the P-gp protein involved in the classical multidrug resistance phenotype. All tumors were stained with pan-beta tubulin antibody and class I tubulin isotype. A majority of the tumor samples expressed class II and class III, although the percentage of positive cells varied significantly between tumors. delta2 alpha tubulin, tau protein and Pgp protein were found in only one tumor sample each. Progression-free survival was shorter (41 days) in patients whose tumors expressed high levels of class III tubulin isotype in comparison to patients with low levels (288 days, p = 0.02). There were 2 responses to chemotherapy among 9 patients (22%) with high levels of class III tubulin vs. 6 among 10 patients (60%) with low levels of expression (Fisher exact test: p = 0.11). These data suggest that high expression of class III tubulin by tumor cells is associated with poor prognosis in patients with NSCLC receiving a taxane-based regimen.
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PMID:Expression of class III beta tubulin in non-small cell lung cancer is correlated with resistance to taxane chemotherapy. 1574 40

Analysis of brain microtubule protein from patients with Alzheimer's disease showed decreased alpha tubulin levels along with increased acetylation of the alpha tubulin subunit, mainly in those microtubules from neurons containing neurofibrillary tau pathology. To determine the relationship of tau protein and increased tubulin acetylation, we studied the effect of tau on the acetylation-deacetylation of tubulin. Our results indicate that tau binds to the tubulin-deacetylase, histone deacetylase 6 (HDAC6), decreasing its activity with a consequent increase in tubulin acetylation. As expected, increased acetylation was also found in tubulin from wild-type mice compared with tubulin from mice lacking tau because of the tau-mediated inhibition of the deacetylase. In addition, we found that an excess of tau protein, as a HDAC6 inhibitor, prevents induction of autophagy by inhibiting proteasome function.
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PMID:Tau--an inhibitor of deacetylase HDAC6 function. 1945 97