Department of Biochemistry and Molecular Biology, School of Medicine, University of Cádiz, Plaza Fragela, 9, 11003, Cádiz, Spain.
J Bioenerg Biomembr. 2009 Dec;41(6):517-21. doi: 10.1007/s10863-009-9250-6.
Complex factors contribute to the appearance of Parkinson's disease (PD), but with a constant mitochondrial involvement. There are two interdependent conditions in PD: brain mitochondrial dysfunction and brain mitochondrial oxidative damage. Mitochondrial dysfunction and reduced complex I activity are recognized in substantia nigra and in frontal cortex in PD patients. The molecular mechanism involved in the inactivation of complex I is likely accounted by the sum of ONOO(-) mediated reactions, reactions with free radical intermediates of the lipid peroxidation process and amine-aldehyde adduction reactions. The inhibitory effects on complex I lead synergistically to denaturation of the protein structure and to further increases of O(2)(-) and ONOO(-) production at the vicinity of complex I. An adaptive response in PD patients has been described with increases in mtNOS activity, mitochondrial mass and mitochondrial biogenesis. Mitochondrial dysfunction in the human frontal cortex is to be considered a factor contributing to impaired cognition in PD.
复杂的因素导致帕金森病（PD）的出现，但始终与线粒体有关。PD 有两种相互依存的情况：大脑线粒体功能障碍和大脑线粒体氧化损伤。PD 患者的黑质和额叶皮层中存在线粒体功能障碍和复合物 I 活性降低。复合物 I 失活所涉及的分子机制可能归因于 ONOO(-)介导的反应、脂质过氧化过程中自由基中间体的反应以及胺-醛加成反应的总和。对复合物 I 的抑制作用协同导致蛋白质结构变性，并在复合物 I 附近进一步增加 O(2)(-)和 ONOO(-)的产生。PD 患者的适应性反应表现为 mtNOS 活性、线粒体质量和线粒体生物发生增加。人类额叶皮层的线粒体功能障碍被认为是 PD 认知障碍的一个因素。
