Mizuno Y, Ikebe S, Hattori N, Nakagawa-Hattori Y, Mochizuki H, Tanaka M, Ozawa T
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
Biochim Biophys Acta. 1995 May 24;1271(1):265-74. doi: 10.1016/0925-4439(95)00038-6.
We discuss the etiology and pathogenesis of Parkinson's disease (PD). Our group and others have found a decrease in complex I of the mitochondrial electron transfer complex in the substantia nigra of patients with PD; in addition, we reported loss of the alpha-ketoglutarate dehydrogenase complex (KGDHC) in the substantia nigra. Dual loss of complex I and the KGDHC will deleteriously affect the electron transport and ATP synthesis; we believe that energy crisis is the most important mechanism of nigral cell death in PD. Oxidative stress has also been implicated as an important contributor to nigral cell death in PD, but we believe that oxidative stress is a secondary phenomenon to respiratory failure, because respiratory failure will increase oxygen free-radical formation and consume glutathione. The primary cause of mitochondrial respiratory failure has not been elucidated yet, but additive effect of environmental neurotoxins in genetically predisposed persons appears to be the most likely possibility.
我们讨论帕金森病（PD）的病因和发病机制。我们团队以及其他研究团队发现，PD患者黑质中线粒体电子传递复合体的复合体I减少；此外，我们报告了黑质中α-酮戊二酸脱氢酶复合体（KGDHC）的缺失。复合体I和KGDHC的双重缺失将对电子传递和ATP合成产生有害影响；我们认为能量危机是PD中黑质细胞死亡的最重要机制。氧化应激也被认为是PD中黑质细胞死亡的重要因素，但我们认为氧化应激是呼吸衰竭的继发现象，因为呼吸衰竭会增加氧自由基的形成并消耗谷胱甘肽。线粒体呼吸衰竭的主要原因尚未阐明，但环境神经毒素在遗传易感性个体中的累加效应似乎是最有可能的原因。
