ROLE OF MITOCHONDRIA IN THE ETIOLOGY AND PATHOGENESIS OF PARKINSONS-DISEASE
ROLE OF MITOCHONDRIA IN THE ETIOLOGY AND PATHOGENESIS OF PARKINSONS-DISEASE
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DOI：
10.1016/0925-4439(95)00038-6
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发表时间：
1995-05-24
影响因子：
6.2
通讯作者：
OZAWA, T
中科院分区：
文献类型：
--
作者：
MIZUNO, Y;IKEBE, S;OZAWA, T
我们讨论了帕金森病（PD）的病因和发病机制。我们的小组和其他人已经发现，减少线粒体电子转移复合物在黑质，口部的PD患者的复合物I;此外，我们报告的α-酮戊二酸脱氢酶复合物（KGDHC）在黑质的损失。复合物I和KGDHC的双重缺失将严重影响电子传递和ATP合成，我们认为能量危机是PD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人群中的叠加效应似乎是最有可能的。
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 ni,ora 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.