Department of Neurology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
Parkinsons Dis. 2011;2011:979231. doi: 10.4061/2011/979231. Epub 2011 Aug 1.
The cellular abnormalities in Parkinson's disease (PD) include mitochondrial dysfunction and oxidative damage, which are probably induced by both genetic predisposition and environmental factors. Mitochondrial dysfunction has long been implicated in the pathogenesis of PD. The recent discovery of genes associated with the etiology of familial PD has emphasized the role of mitochondrial dysfunction in PD. The discovery and increasing knowledge of the function of PINK1 and parkin, which are associated with the mitochondria, have also enhanced the understanding of cellular functions. The PINK1-parkin pathway is associated with quality control of the mitochondria, as determined in cultured cells treated with the mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP), which causes mitochondrial depolarization. To date, the use of mitochondrial toxins, for example, 1-methyl-4-phynyl-tetrahydropyridine (MPTP) and CCCP, has contributed to our understanding of PD. We review how these toxins and familial PD gene products are associated with and have enhanced our understanding of the role of mitochondrial dysfunction in PD.
帕金森病（PD）中的细胞异常包括线粒体功能障碍和氧化损伤，这可能是由遗传易感性和环境因素共同引起的。线粒体功能障碍长期以来一直被认为与 PD 的发病机制有关。最近发现与家族性 PD 病因相关的基因，强调了线粒体功能障碍在 PD 中的作用。对与线粒体相关的 PINK1 和 parkin 功能的发现和不断增加的了解，也增强了对细胞功能的理解。PINK1-parkin 途径与线粒体的质量控制有关，这在培养细胞中用线粒体解偶联剂羰基氰化物 m-氯苯腙（CCCP）处理后得到证实，CCCP 会导致线粒体去极化。迄今为止，线粒体毒素的使用，例如 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）和 CCCP，有助于我们了解 PD。我们回顾了这些毒素和家族性 PD 基因产物如何与线粒体功能障碍在 PD 中的作用相关联，并增强了我们对其作用的理解。
