Jenner P, Schapira A H, Marsden C D
RKQ (Royal Kings and Queens) Parkinson's Disease Research Group, King's College, London, UK.
Neurology. 1992 Dec;42(12):2241-50. doi: 10.1212/wnl.42.12.2241.
Current concepts as to the cause of Parkinson's disease (PD) suggest an inherited predisposition to environmental or endogenous toxic agents. Study of the substantia nigra after death in PD has highlighted three major changes: (1) evidence of oxidative stress and depletion of reduced glutathione; (2) high levels of total iron, with reduced ferritin buffering; and (3) mitochondrial complex I deficiency. Which of these is the primary event, generating a secondary cascade of changes culminating in nigral cell death, is unknown. In presymptomatic Lewy body-positive control brains, the nigra shows depletion of reduced glutathione content and, possibly, a reduction of complex I activity. Whatever the significance of these various abnormalities, be they causal or secondary, they provide novel targets for the development of new strategies to treat the cause of PD.
目前关于帕金森病（PD）病因的观点认为，患者存在对环境或内源性有毒物质的遗传易感性。对帕金森病患者死后黑质的研究突出了三个主要变化：（1）氧化应激和还原型谷胱甘肽消耗的证据；（2）总铁水平升高，铁蛋白缓冲能力降低；（3）线粒体复合体I缺乏。这些变化中哪一个是引发继发性变化级联反应并最终导致黑质细胞死亡的主要事件尚不清楚。在症状前路易体阳性的对照大脑中，黑质显示还原型谷胱甘肽含量减少，并且可能复合体I活性降低。无论这些各种异常的意义如何，无论是因果关系还是继发性的，它们都为开发治疗帕金森病病因的新策略提供了新的靶点。
