期刊
NEUROBIOLOGY OF DISEASE
卷 21, 期 1, 页码 69-79出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2005.06.010
关键词
familial amyotrophic lateral sclerosis; mitochondria; neuro-degeneration; oxidative stress; superoxide dismutase
资金
- Telethon [GGP030066] Funding Source: Medline
Several studies have indicated that apoptotic pathways are responsible for the loss of motor neurons that constitute the hallmark of amyotrophic lateral sclerosis (ALS). In this study, we demonstrate that apoptosis induced by the expression of several mutant Cu,Zn superoxide dismutases (SOD 1) typical of familial ALS is mediated by Apaf1, a scaffold protein involved in neural development. Using, different cell lines of neuronal origin and modulating the expression of both mutant SOD1s and Apaf1, we show that the removal of Apaf1 prevents cells death. Interestingly, intercepting activation of the caspases cascade is also effective in preventing both the mitochondrial damage and the increase in the production of reactive oxygen species induced by fALS-SOD1, even in the presence of cytochrome c release, This death pathway may be crucial also for the pathogenesis of the sporadic form of the disease, where markers of increased oxidative stress and mitochondria damage have been found. (c) 2005 Elsevier Inc. All rights reserved.
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