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

被引:33
作者
Jiang, Xue [1 ]
Jin, Tao [1 ]
Zhang, Haining [1 ]
Miao, Jing [1 ]
Zhao, Xiuzhen [1 ]
Su, Yana [1 ]
Zhang, Ying [1 ]
机构
[1] Jilin Univ, Dept Neurol, Hosp 1, Xinmin St 71, Changchun 130000, Jilin, Peoples R China
关键词
ALPHA-SYNUCLEIN; OXIDATIVE STRESS; DYNAMICS; PINK1; BIOGENESIS; MITOPHAGY; AUTOPHAGY; FUSION; DEGRADATION; PGC-1-ALPHA;
D O I
10.1155/2019/4578462
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 (alpha-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.
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页数:11
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