Tretter Laszlo, Sipos Ildiko, Adam-Vizi Vera
Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary.
Neurochem Res. 2004 Mar;29(3):569-77. doi: 10.1023/b:nere.0000014827.94562.4b.
Oxidative stress and partial deficiencies of mitochondrial complex I appear to be key factors in the pathogenesis of Parkinson's disease. They are interconnected; complex I inhibition results in an enhanced production of reactive oxygen species (ROS), which in turn will inhibit complex I. Partial inhibition of complex I in nerve terminals is sufficient for in situ mitochondria to generate more ROS. H2O2 plays a major role in inhibiting complex I as well as a key metabolic enzyme, alpha-ketoglutarate dehydrogenase. The vicious cycle resulting from partial inhibition of complex I and/or an inherently higher ROS production in dopaminergic neurons leads over time to excessive oxidative stress and ATP deficit that eventually will result in cell death in the nigro-striatal pathway.
氧化应激和线粒体复合体I的部分缺陷似乎是帕金森病发病机制中的关键因素。它们相互关联；复合体I的抑制会导致活性氧（ROS）生成增加，而ROS反过来又会抑制复合体I。神经末梢中复合体I的部分抑制足以使原位线粒体产生更多的ROS。过氧化氢在抑制复合体I以及关键代谢酶α-酮戊二酸脱氢酶方面发挥着主要作用。多巴胺能神经元中复合体I的部分抑制和/或固有较高的ROS产生所导致的恶性循环，随着时间的推移会导致过度的氧化应激和ATP缺乏，最终将导致黑质纹状体通路中的细胞死亡。
