Roles of autophagy-mediated alpha-synuclein clearance in the development of Parkinson disease
10.3760/cma.j.cn371468-20231128-00271
- VernacularTitle:自噬介导α-突触核蛋白清除在帕金森病发生发展中的作用
- Author:
Haojie ZHANG
1
;
Meng HOU
;
Tingting GUO
;
Li WANG
Author Information
1. 山西医科大学附属第二医院神经内科，太原 030000
- Keywords:
α-Synuclein;
Autophagy;
Parkinson disease;
Neurodegenerative diseases;
Neuroinflammation
- From:
Chinese Journal of Behavioral Medicine and Brain Science
2024;33(3):219-224
- CountryChina
- Language:Chinese
-
Abstract:
Parkinson disease (PD) is a common chronic neurodegenerative disease that seriously affects the quality of life of patients and has become an important population health problem in society.The typical neuropathological feature of PD is the abnormal aggregation of α-synuclein (α-Syn) in the substantia nigra-striatal region, causing dopaminergic degenerative necrosis of neurons. With further research, it was found that cellular autophagy mediated the clearance process of pathological α-Syn involved in the pathogenesis of PD. Autophagy is an important pathway for cells to remove abnormal aggregated proteins and senescence-damaged organelles, and autophagic removal of abnormal α-Syn deposition can maintain cellular homeostasis and protect dopaminergic neurons. In addition, impaired autophagy causes α-Syn aggregation, increases α-Syn propagation in the brain, promotes the degeneration of dopaminergic neurons, and is involved in the development of PD.PD-related genes affect autophagy regulation, and mutations in related genes can lead to impaired lysosomal function to block autophagy. At the same time, abnormal aggregation of α-Syn further disrupts the autophagy process, reduces the autophagic clearance capacity, and increases the accumulation of neurotoxicity. Impaired autophagy and abnormal α-Syn aggregation are important mechanisms of degeneration in nigrostriatal dopaminergic neurons. Therefore, studies targeting autophagy and abnormal α-Syn aggregation may provide new ideas for the pathogenesis of PD, and reducing α-Syn accumulation by increasing autophagic flux may become a key target for the treatment of PD.
