Department of Neurology, University of Florida, Gainesville, FL 32610, USA.
Department of Neurology, University of Florida, Gainesville, FL 32610, USA.
Brain Res. 2021 Sep 15;1767:147434. doi: 10.1016/j.brainres.2021.147434. Epub 2021 Mar 19.
Parkinson's disease (PD) is a progressive neurodegenerative disease manifesting both motor and non-motor symptoms. The motor features are generally ascribed to the selective loss of dopamine neurons within the substantia nigra pars compacta. While the precise etiology of PD remains elusive, multiple genetic and environmental elements have emerged as contributing factors. The discovery of MPTP-induced parkinsonism directed intense inquiry towards mitochondrial pathways, with a specific focus on mitochondrial complex I. Consisting of more than 40 subunits, complex I is the first enzyme of the electron transport chain that is required for mitochondrial ATP production. In this review, we present a critical analysis of studies assessing the prevalence and specificity of mitochondrial complex I deficiency in PD. In addition, we take the novel view of incorporating the features of genetically-defined bona fide complex I disorders and the prevalence of nigral involvement in such cases. Through this innovative bi-directional view, we consider both complex I changes in a disease of the substantia nigra and nigral changes in diseases of complex I. We assess the strength of association between nigral cell loss and complex I deficits, as well as the oft under-appreciated heterogeneity of complex I deficiency disorders and the variability of the PD data.
帕金森病（PD）是一种进行性神经退行性疾病，表现出运动和非运动症状。运动特征通常归因于黑质致密部中多巴胺神经元的选择性丧失。虽然 PD 的确切病因仍然难以捉摸，但已经出现了多种遗传和环境因素作为促成因素。MPTP 诱导的帕金森病的发现促使人们对线粒体途径进行了深入研究，特别是对线粒体复合物 I 进行了研究。复合物 I 由 40 多个亚基组成，是电子传递链中的第一个酶，是线粒体 ATP 产生所必需的。在这篇综述中，我们对评估 PD 中线粒体复合物 I 缺乏的患病率和特异性的研究进行了批判性分析。此外，我们还采用了一种新颖的观点，即将遗传定义的真正复合物 I 疾病的特征和此类病例中黑质受累的情况纳入考虑。通过这种创新的双向观点，我们同时考虑了黑质中复合物 I 的变化以及复合物 I 疾病中的黑质变化。我们评估了黑质细胞丧失与复合物 I 缺陷之间的关联强度，以及复合物 I 缺陷疾病的异质性和 PD 数据的可变性常常被低估的情况。
