Research progress on the pathogenic mechanisms of α-synuclein and related disease models
10.3969/j.issn.1005-4847.2025.09.010
- VernacularTitle:α-突触核蛋白致病机制及其疾病模型研究进展
- Author:
Yuandong LIN
1
;
Yawen JIANG
;
Xiangxing ZHU
;
Chunling LU
;
Tao WANG
;
Yingshan CHEN
;
Dongsheng TANG
Author Information
1. 佛山大学医学院广东省基因编辑工程技术研究中心,广东佛山 528225;广东药康生物科技有限公司,广东佛山 528000
- Publication Type:Journal Article
- Keywords:
α-synuclein;
oligomers;
dopaminergic neurons;
substantia nigra;
gut-brain axis
- From:
Acta Laboratorium Animalis Scientia Sinica
2025;33(9):1340-1359
- CountryChina
- Language:Chinese
-
Abstract:
The core pathological feature of Parkinson's disease(PD)is the abnormal aggregation of α-synuclein and the result ing neuronal damage.α-Synuclein exhibits toxic effects when it forms oligomers or fibrils,leading to neuronal death via multiple pathways,including mitochondrial dysfunction,impaired vesicular trafficking,dopamine auto-oxidation,and neuroinflammation.In addition,α-synuclein can propagate between cells via exosomes,endocytosis/exocytosis,tunneling nanotubes,or vagal nerve axonal transport,creating a cascade of pathological effects.Animal models of PD that recapitulate the key pathological hallmark of α-synuclein accumulation are indispensable tools for elucidating disease mechanisms and developing novel therapeutic interventions.To date,various strategies,including transgenic techniques,bacterial artificial chromosome(BAC)-mediated expression,viral vector-mediated overexpression,and gene editing,have been employed to develop α-synuclein overexpression animal models.These models have significantly advanced our exploration of the relationship between PD and α-synuclein.This systematic review considers the structure and function of α-synuclein,its mechanisms of toxicity,intercellular propagation pathways,animal models of overexpression,and potential therapeutic targets based on its pathogenic mechanisms.
