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)

In Alzheimer's Disease brain, the microtubule-associated protein tau is hyperphosphorylated at specific epitopes and abnormally aggregates into filamentous structures. In addition, there is significant neurodegeneration in Alzheimer's disease brain, and there is data to suggest that apoptotic-like processes may contribute to the neurodegeneration. It has been demonstrated that in PC12 cells undergoing apoptosis due trophic factor removal, tau is hyperphosphorylated prior to chromatin condensation. To establish that increased tau phosphorylation is a generalized outcome of the apoptotic process, and to examine the involvement of the protein kinase in these events, apoptosis was induced in retinoic-acid differentiated human SH-SY5Y neuroblastoma cells using the topoisomerase-1 inhibitor camptothecin. Treatment of the differentiated SH-SY5Y cells with camptothecin resulted in a time and concentration dependent activation of caspase-3 with a concomitant increase in the presence of apoptotic nuclei. Immunoblotting revealed that camptothecin treatment resulted in a significant increase in tau phosphorylation. Addition of a cyclin-dependent kinase inhibitor reduced camptothecin-induced cell death in the differentiated SH-SY5Y cells and decreased the effects of camptothecin on tau phosphorylation. In contrast, a general caspase inhibitor decreased camptothecin-induced cell death, but did not significantly decrease the increases in tau phosphorylation. These results suggest that increased tau phosphorylation is likely a generalized outcome of apoptotic processes in neuron-related cells, and that cyclin-dependent kinases probably play a role in this process.
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PMID:Tau phosphorylation during apoptosis of human SH-SY5Y neuroblastoma cells. 1172 Jul 9

Gene expression analysis in breast cancer patients undergoing neoadjuvant chemotherapy is an interesting tool for identification of gene signatures and new markers to predict tumor response. However, the detection of predictive markers strongly depends on the drugs used in the specific therapeutic setting. There is growing evidence that topoisomerase II-alpha (TOPO IIalpha) is a marker for anthracycline-, and microtubule-associated protein tau (MAPT) for taxane sensitivity. HER-2 has been described as a marker of both anthracycline and taxane sensitivity. We performed gene expression profiling of 50 patients within the GEPARTRIO study, an anthracycline and taxane neoadjuvant chemotherapy trial. Here we investigate the predictive value of TOPO IIalpha, MAPT and HER-2 mRNA expression for pathological complete response (pCR) in this setting. Interestingly, HER-2 gene expression was strongly predictive of pCR (P=0.017) as well as overall response (P=0.037) and clinical complete response (cCR, P=0.050). In contrast, for both TOPO IIalpha and MAPT no correlation with pCR was observed in our sample group.
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PMID:Gene expression profiling of breast cancer patients treated with docetaxel, doxorubicin, and cyclophosphamide within the GEPARTRIO trial: HER-2, but not topoisomerase II alpha and microtubule-associated protein tau, is highly predictive of tumor response. 1701 Jun 9