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)

The causes and the mechanisms of neuronal death in Alzheimer's disease are not elucidated, although some new insights have been proposed over the past years, including free-radical toxicity, beta-amyloid toxicity, excitotoxicity, and disturbed cellular calcium metabolism. Some authors have also pointed out that apoptosis could play a role in neuronal degeneration, but it is still largely debated. Here, we review some recent data linking the induction of experimental neuronal apoptosis in vitro and the molecular pathology of the tau protein and amyloid precursor protein (APP). In cultures exposed to mild glutamate toxicity, tau mRNA expression, not beta-actin, is enhanced in stressed neurons. The Guam cycad toxin metabolite methylazoxymethanol also produces an increase of tau gene transcription that exacerbates changes induced by glutamate. In serum-deprived cultures or glutamate-exposed cultures, neurons committed to apoptosis have a reduced tau gene expression, whereas resistant neurons display a stable or even augmented tau mRNA expression accompanied by a persistent tau phosphorylation near serine 202. In the same conditions, stressed neurons produce membrane blebbings strongly immunopositive for APP and putative amyloidogenic fragments that are subsequently released in the extracellular space. Experimental apoptosis in neurons can recapitulate tau and APP modifications that could be associated with a selective vulnerability and a progression of cellular degeneration along the neuronal network.
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PMID:Toxic neuronal apoptosis and modifications of tau and APP gene and protein expressions. 1046 44

Cytoskeletal components play an important role in maintaining cellular architecture and internal organization, with clear involvement of defining cell shape, in cell division and other cellular processes, such as neurite extension and maintenance. Alterations of cytoskeleton in human neuroblastoma SK-N-SH cells after exposure to different concentrations of tri-ocresyl phosphate (TOCP) for 12 hr were investigated. TOCP decreased the cell viability in a dose-dependent manner; the viability of SK-N-SH was reduced to approximately 50% of baseline after a 12-hour exposure to TOCP at high concentration (5 mM). Biochemical characterization by western blotting revealed that 1 and 5 mM concentrations of TOCP significantly inhibited the expression of neurofilament high molecular weight protein (NF-H), and that 5 mM TOCP inhibited expression of microtubule-associated protein 2c and tau protein, but not beta-actin. Indirect immunofluorescence analysis revealed that higher concentrations of TOCP decreased the length of neuritis and changed the structure of microfilaments, which are associated with NF-H. In addition, activities of neuropathy target esterase and acetylcholinesterase were significantly reduced after exposure to 5 mM TOCP for 12 hr. Together, these results suggested that the loss of cytoskeletal components is the early event during the process of TOCP toxicity towards human neuroblastoma SK-N-SH cells.
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PMID:Effect of tri-o-cresyl phosphate on cytoskeleton in human neuroblastoma SK-N-SH cell. 1690 9

Syncytiotrophoblast formation is affected by a number of pathological conditions and suppressed syncytiotrophoblast formation due to hypoxia may play a role in the pathogenesis of preeclampsia. However, the molecular basis of hypoxia-inhibited trophoblast syncytialization is poorly understood. To determine the effect of hypoxia on trophoblast syncytialization, a proteomic analysis was performed in the human cytotrophoblast cell line BeWo using two-dimensional electrophoresis and MALDI-TOF-TOF-MS. Hypoxia induced marked inhibition of BeWo cell fusion and differentiation. The proteomic profiling was established under hypoxia in BeWo cell syncytialization. The results showed that twenty proteins were significantly up-or down-regulated under hypoxia, compared with cells under normoxia. In response to hypoxia, three antioxidants, peroxiredoxin 1, peroxiredoxin 2 and 1-Cys peroxiredoxin, were down-regulated, two proteins involved in glycolysis pathway (malate dehydrogenase and enolase) were up-regulated. The expression of two members of the annexin family (annexin A2 and annexin A5) increased. We also found a decreased expression of 14-3-3 tau protein in hypoxia treated cells. Proteins implied in protein degradation and folding were also identified. The expression of two cytoskeleton components (keratin 1 and beta-actin) was found to be down-regulated. In addition, galectin-3 was up-regulated. These proteins have been implicated in regulating cellular oxidative stress, glycolysis, signal transduction, protein folding and degradation, cell mobility and cytoskeletal structure formation. Western blot analysis revealed that the levels of peroxiredoxin 1 and 14-3-3 tau decreased, whereas the levels of annexin A5 and annexin A2 increased in BeWo cells under hypoxia. These findings provided new insights into the molecular mechanisms in mediating cellular response to hypoxia in trophoblast syncytialization.
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PMID:Proteomic analysis of hypoxia-induced responses in the syncytialization of human placental cell line BeWo. 1709 81

The deposition of highly phosphorylated microtubule-associated tau protein has been observed in ALS with cognitive impairment (ALSci). In these studies, we have examined whether the expression of two candidate protein kinases for mediating tau hyperphosphorylation (GSK3beta or CDK5) are also altered. The expression of GSK, CDK and p25/p35 was assayed in human frontal, hippocampal, cerebellar, cervical (dorsal and ventral) and lumbar (dorsal and ventral) tissue from neurologically intact control (5), ALS (5) or ALSci (5) patients using RT-PCR, Western blot or immunohistochemistry. To assess GSK-3beta activity, we examined GSK3beta, phospho-GSK3beta and phospho-beta-catenin expression. Expression levels relative to that of beta-actin were compared by ANOVA. The expression of GSK, GSK3beta and phospho-GSK3beta was increased in both ALS and ALSci compared to that of the control. This was accompanied by an increased expression of phospho-beta-catenin. No significant difference between control, ALS or ALSci was observed with respect to the expression of CDK5 or p25/p35. Both GSK3beta and phospho-GSK3beta immunoreactive neurons were mainly located in layer II and layer III in the frontal cortex and in layer II in the hippocampus. This was consistent with the previously described distribution of hyperphosphorylated tau bearing neurons in ALS and ALSci. These data suggest that GSK3beta expression is upregulated in ALS and ALSci and that GSK3beta activation is associated with the intraneuronal deposition of hyperphosphorylated tau protein. This supports the potential role for GSK3beta as a therapeutic target in ALS.
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PMID:Upregulation of GSK3beta expression in frontal and temporal cortex in ALS with cognitive impairment (ALSci). 1822 34