期刊
JOURNAL OF NEUROIMMUNOLOGY
卷 233, 期 1-2, 页码 18-28出版社
ELSEVIER
DOI: 10.1016/j.jneuroim.2010.10.036
关键词
SurR9-C84A; Neuroprotection; Multiple sclerosis; Neuro-degeneration
资金
- Institute for Technology Research and Innovation (ITRI), Deakin University
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. Crown Copyright (C) 2010 Published by Elsevier B.V. All rights reserved.
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