Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
J Bioenerg Biomembr. 2009 Dec;41(6):493-7. doi: 10.1007/s10863-009-9249-z.
Mitochondrial impairment has been collecting more and more attention as a contributing factor to the etiology of Parkinson's disease. Above all, the NADH-quinone oxidoreductase, complex I, of the respiratory chain seems to be most culpable. Complex I dysfunction is translated to an increased production of reactive oxygen species and a decreased energy supply. In the brain, the dopaminergic neurons are one of the most susceptible cells. Their death is directly linked to the disease apparition. Developing an effective gene therapy is challenged by harmful actions of reactive oxygen species. To overcome this problem a therapeutic candidate must be able to restore the NADH-quinone oxidoreductase activity regardless of how complex I is impaired. Here we discuss the potency of the yeast alternative NADH dehydrogenase, the Ndi1 protein, to reinstate the mitochondrial respiratory chain compensating for disabled complex I and the benefit Ndi1 brings toward retardation of Parkinson's disease.
线粒体损伤作为帕金森病病因的一个促成因素，越来越受到关注。首先，呼吸链中的 NADH-醌氧化还原酶，复合物 I，似乎是最有责任的。复合物 I 功能障碍导致活性氧的产生增加和能量供应减少。在大脑中，多巴胺能神经元是最易受影响的细胞之一。它们的死亡与疾病的出现直接相关。开发有效的基因治疗受到活性氧的有害作用的挑战。为了克服这个问题，治疗候选物必须能够恢复 NADH-醌氧化还原酶的活性，而不管复合物 I 受到怎样的损伤。在这里，我们讨论了酵母替代 NADH 脱氢酶，即 Ndi1 蛋白，恢复线粒体呼吸链的能力，补偿功能失调的复合物 I，并为减缓帕金森病带来益处。
