Mitochondria in neurodegenerative disorders: regulation of the redox state and death signaling leading to neuronal death and survival

作者：Naoi Makoto^*; Maruyama Wakako; Yi Hong; Inaba Keiko; Akao Yukihiro; Shamoto Nagai Masayo

来源：Journal of Neural Transmission, 2009, 116(11): 1371-1381.

DOI：10.1007/s00702-009-0309-7

• Apoptosis
• Mitochondria
• Oxidative stress
• Redox state
• Neuroprotection
• MAO inhibitor

In Parkinson's disease, impaired function of mitochondrial complex I is involved in selective degeneration of dopamine neurons in the substantia nigra. Mitochondria are now considered to play an active role in neuronal death process through activating "intrinsic" apoptotic signaling, in addition to production of reactive oxygen species. This paper presents our recent findings on new functions of mitochondria in regulation of their redox state and function through reversible "S-glutathionylation", a mixed disulfide binding between sulfhydryl groups of GSH and protein cysteine in complex I subunits. Type A monoamine oxidase (MAO-A) localized at the mitochondrial outer membrane is a binding site of neurotoxins leading to apoptosis. Rasagiline and (-)deprenyl, type B MAO inhibitors of propagylamine-derivatives, bind to MAO-A to protect neuronal cells against apoptosis through induction of pro-survival Bcl-2 and neurotrophic factors. This review discusses the new role of mitochondria in regulation of neuronal cell death of neurodegenerative disorders.

• 出版日期2009-11