Mitochondria-derived reactive oxygen species mediate caspase-dependent and -independent neuronal deaths.
Mitochondria-derived reactive oxygen species mediate caspase-dependent and -independent neuronal deaths.
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DOI：
10.1016/j.mcn.2014.09.002
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Franklin JL
中科院分区：
文献类型：
--
作者：
McManus MJ;Murphy MP;Franklin JL
Mitochondrial dysfunction and oxidative stress are implicated in many neurodegenerative diseases. Mitochondria-targeted drugs that effectively decrease oxidative stress, protect mitochondrial energetics, and prevent neuronal loss may therefore lend therapeutic benefit to these currently incurable diseases. To investigate the efficacy of such drugs, we examined the effects of mitochondria-targeted antioxidants MitoQ10 and MitoE2 on neuronal death induced by neurotrophin deficiency. Our results indicate that MitoQ10 blocked apoptosis by preventing increased mitochondria-derived reactive oxygen species (ROS) and subsequent cytochrome c release, caspase activation, and mitochondrial damage in nerve growth factor (NGF)-deprived sympathetic neurons, while MitoE2 was largely ineffective. In this paradigm, the most proximal point of divergence was the ability of MitoQ10 to scavenge mitochondrial superoxide (O2•−). MitoQ10 also prevented caspase-independent neuronal death in these cells demonstrating that the mitochondrial redox state significantly influences both apoptotic and nonapoptotic pathways leading to neuronal death. We suggest that mitochondria-targeted antioxidants may provide tools for delineating the role and significance of mitochondrial ROS in neuronal death and provide a new therapeutic approach for neurodegenerative conditions involving trophic factor deficits and multiple modes of cell death.
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DOI：
10.1083/jcb.200302109
发表时间：
2003-07-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chang LK;Schmidt RE;Johnson EM Jr
通讯作者：
Johnson EM Jr
影响因子：
7.4
作者：
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通讯作者：
Aw, Tak Yee
影响因子：
10.6
作者：
Duchen, Michael R.
通讯作者：
Duchen, Michael R.
影响因子：
3.9
作者：
Chang, LK;Putcha, GV;Johnson, EM
通讯作者：
Johnson, EM
影响因子：
16.2
作者：
Deshmukh, M;Johnson, EM
通讯作者：
Johnson, EM