کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6021156 | 1580440 | 2011 | 11 صفحه PDF | دانلود رایگان |

Currently, there are no known treatments for protection of axonal loss associated with neuroinflammatory diseases such as multiple sclerosis (MS). Survivin is a member of the inhibitors of the apoptosis (IAP) family of proteins that its neuroprotective effects have not been studied. We demonstrate here that SurR9-C84A, a survivin mutant, exhibits a neuroprotective role against the cytotoxic effects of activated T-cell infiltrates, such as granzyme B (GrB). The activated T-cell supernatants induce toxicity on differentiated SK-N-SH cells, which is associated with the loss of Ca2+ homeostasis, the increased population of dead cells, mitochondrial membrane depolarisation, and the accelerated expression of cyclinD1, caspase3 and Fas, as observed for most apoptotic cells. Alternatively, the pre-treatment with SurR9-C84A reduces the population of dead cells by balancing the cytosolic Ca2+ homeostasis, decreasing the level of mitochondrial depolarisation, and also reducing the expression of cyclinD1 and caspase3. Our findings suggest that SurR9-C84A has a neuroprotective effect against the cytotoxins existing in activated T-cell supernatants including GrB.
Journal: Journal of Neuroimmunology - Volume 233, Issues 1â2, April 2011, Pages 18-28