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Current Progress of Mitochondrial Quality Control Pathways Underlying the Pathogenesis of Parkinson’s Disease

机译：帕金森病发病机制下的线粒体质量控制途径进展

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Parkinson’s disease (PD), clinically characterized by motor and nonmotor symptoms, is a common progressive and multisystem neurodegenerative disorder, which is caused by both genetic and environmental risk factors. The main pathological features of PD are the loss of dopaminergic (DA) neurons and the accumulation of alpha-synuclein (α-syn) in the residual DA neurons in the substantia nigra pars compacta (SNpc). In recent years, substantial progress has been made in discovering the genetic factors of PD. In particular, a total of 19 PD-causing genes have been unraveled, among which some members have been regarded to be related to mitochondrial dysfunction. Mitochondria are key regulators of cellular metabolic activity and are critical for many important cellular processes including energy metabolism and even cell death. Their normal function is basically maintained by the mitochondrial quality control (MQC) mechanism. Accordingly, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a kind of neurotoxin, exerts its neurotoxic effects at least partially by producing its toxic metabolite, namely, 1-methyl-4-phenylpyridine (MPP+), which in turn causes mitochondrial dysfunction by inhibiting complex I and mimicking the key features of PD pathogenesis. This review focused on three main aspects of the MQC signaling pathways, that is, mitochondrial biogenesis, mitochondrial dynamics, and mitochondrial autophagy; hence, it demonstrates in detail how genetic and environmental factors result in PD pathogenesis by interfering with MQC pathways, thereby hopefully contributing to the discovery of novel potential therapeutic targets for PD.
机译：帕金森病（PD），临床以电机和非运动症状为特征，是一种常见的渐进和多系统神经变性障碍，这是由遗传和环境风险因素引起的。 Pd的主要病理特征是多巴胺能（DA）神经元的丧失，并且在体积NIGRACACTA（SNPC）中残留DA神经元中的α-突触核蛋白（α-SYN）的积累。近年来，在发现PD的遗传因素方面取得了实质性进展。特别地，已经解开了总共19个PD引起的基因，其中一些成员被认为与线粒体功能障碍有关。线粒体是细胞代谢活性的关键调节因子，对于许多重要的细胞过程至关重要，包括能量代谢甚至细胞死亡。它们的正常功能基本上由线粒体质量控制（MQC）机制维持。因此，1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP），一种神经毒素，至少部分地通过产生其毒性代谢物，即1-甲基-4-苯基吡啶来施加其神经毒性作用（MPP +），其又通过抑制复合物I和模拟PD发病机制的关键特征来引起线粒体功能障碍。本综述专注于MQC信号传导途径的三个主要方面，即线粒体生物发生，线粒体动力学和线粒体自噬。因此，它详细阐述了遗传和环境因素通过干扰MQC途径是如何导致PD发病机制，从而有望对PD的新潜在治疗靶点产生贡献。

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