Department of Neurobiology School of Basic Medical Sciences, Beijing Institute for Brain Disorders, Capital Medical University, Beijing 100069, China.
Center of Parkinson's Disease Beijing Key Laboratory of Neural Regeneration and Repair, Beijing Key Laboratory on Parkinson's Disease, Key Laboratory for Neurodegenerative Disease of the Ministry of Education, Beijing 100069, China.
Cells. 2019 Jul 12;8(7):712. doi: 10.3390/cells8070712.
Parkinson's disease (PD) is the second most common neurodegenerative disease. The pathogenesis of PD is complicated and remains obscure, but growing evidence suggests the involvement of mitochondrial and lysosomal dysfunction. Mitophagy, the process of removing damaged mitochondria, is compromised in PD patients and models, and was found to be associated with accelerated neurodegeneration. Several PD-related proteins are known to participate in the regulation of mitophagy, including PINK1 and Parkin. In addition, mutations in several PD-related genes are known to cause mitochondrial defects and neurotoxicity by disturbing mitophagy, indicating that mitophagy is a critical component of PD pathogenesis. Therefore, it is crucial to understand how these genes are involved in mitochondrial quality control or mitophagy regulation in the study of PD pathogenesis and the development of novel treatment strategies. In this review, we will discuss the critical roles of mitophagy in PD pathogenesis, highlighting the potential therapeutic implications of mitophagy regulation.
帕金森病(PD)是第二常见的神经退行性疾病。PD 的发病机制复杂且仍不清楚,但越来越多的证据表明线粒体和溶酶体功能障碍的参与。自噬,即清除受损线粒体的过程,在 PD 患者和模型中受到损害,并且与加速的神经退行性变有关。已知几种与 PD 相关的蛋白质参与自噬的调节,包括 PINK1 和 Parkin。此外,几种与 PD 相关的基因突变通过扰乱自噬导致线粒体缺陷和神经毒性,表明自噬是 PD 发病机制的关键组成部分。因此,在研究 PD 的发病机制和开发新的治疗策略时,了解这些基因如何参与线粒体质量控制或自噬调节至关重要。在这篇综述中,我们将讨论自噬在 PD 发病机制中的关键作用,强调自噬调节的潜在治疗意义。