Novel survivin mutant protects differentiated SK-N-SH human neuroblastoma cells from activated T-cell neurotoxicity

作者：Baratchi Sara; Kanwar Rupinder K; Kanwar Jagat R^*

来源：Journal of Neuroimmunology, 2011, 233(1-2): 18-28.

DOI：10.1016/j.jneuroim.2010.10.036

• SurR9-C84A
• Neuroprotection
• Multiple sclerosis
• Neuro-degeneration

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 Ca(2+) 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 Ca(2+) 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.

• 出版日期2011-4
• 单位迪肯大学