中国全科医学2026，Vol.29Issue(23)：3268-3274,7.DOI:10.12114/j.issn.1007-9572.2025.0392
帕金蛋白在代谢相关脂肪性肝病中的潜在非经典功能及治疗展望
The Non-canonical Functions and Therapeutic Prospects of Parkin in Metabolic Associated Fatty Liver Disease
摘要
Abstract
Metabolic associated fatty liver disease(MAFLD),as the most prevalent chronic liver disease worldwide,features a complex and multifactorial pathogenesis,and no targeted therapeutics are currently available.This review focuses on the E3 ubiquitin ligase Parkin,providing a systematic analysis of its classical and non-classical functions during MAFLD progression.We particularly highlight Parkin's pivotal roles in multiple pathological processes,including the regulation of apoptosis and pyroptosis,mediation of endoplasmic reticulum-mitochondria crosstalk,reprogramming of lipid metabolism,and modulation of hepatic stellate cell activation.It is well established that Parkin-mediated mitophagy via the PINK1/Parkin pathway serves as a central mechanism for maintaining hepatic metabolic homeostasis and suppressing inflammatory responses.However,growing evidence from cross-disease model studies suggests that under lipotoxic stress,Parkin's functional repertoire extends far beyond mitochondrial quality control.Building on this evidence,we propose that Parkin likely participates may potentially participate in multiple MAFLD pathogenic pathways through a series of non-canonical ubiquitination events.Consequently,future therapeutic strategies in MAFLD should aim at coordinated multi-pathway intervention.This perspective opens new avenues for innovative drug discovery targeting Parkin.关键词
代谢相关脂肪性肝病/帕金蛋白/线粒体自噬/泛素化/综述Key words
Metabolic associated fatty liver disease/Parkin/Mitophagy/Ubiquitination/Review分类
医药卫生引用本文复制引用
阮何静,赵文,李龙灿,赵久法,李冬冬..帕金蛋白在代谢相关脂肪性肝病中的潜在非经典功能及治疗展望[J].中国全科医学,2026,29(23):3268-3274,7.基金项目
国家自然科学基金面上项目(82570714) （82570714）
