摘要
脑内蛋白质的合成与降解处于动态平衡之中。自噬-溶酶体途径(autophagy-lysosome pathway,ALP)是细胞内主要的降解途径,能够通过及时降解错误折叠、聚集和损伤的蛋白质来维持细胞稳态。ALP降解功能的异常可导致机体内β-淀粉样蛋白(amyloid β-protein,Aβ)和磷酸化Tau蛋白的沉积,出现记忆、学习等多认知域的损伤,这种病理改变与阿尔茨海默病(Alzheimer's disease,AD)的发病机制密切相关。中医学认为“肾精亏虚,痰浊蒙窍”是AD发生的核心病机,“痰浊”是疾病发生、发展的病理基础。现代医学研究发现“痰浊”与Aβ的生成与清除失衡以及Tau蛋白过度磷酸化有关,“化痰开窍”与降解异常蛋白聚集有着不谋而合之处。文章梳理近年国内外文献,对自噬与AD特征性神经病理改变的相互作用、自噬相关信号通路对AD的调控机制以及中医从“痰浊”论治的相关性研究作以综述,旨在从调控自噬的角度为临床改善AD提供新的研究方向和治疗靶点。
The synthesis and degradation of proteins in the brain are maintained in a dynamic equilibrium.The autophagy-lysosome pathway(ALP)is a crucial intracellular degradation pathway that efficiently eliminates misfolded,aggregated,and damaged proteins to preserve cellular homeostasis.Dysfunctional ALP can result in the accumulation of amyloidβ-protein(Aβ)and phosphorylated Tau protein,leading to impairments in multiple cognitive domains such as memory and learning.These pathological changes are closely associated with the pathogenesis of Alzheimer's disease(AD).Traditional Chinese medicine posits that AD is primarily caused by“kidney essence deficiency”and“phlegm turbidness”,with the latter serving as the underlying basis for disease occurrence and progression.Modern medical research has revealed that“phlegm turbidness”is linked to imbalances in Aβproduction and clearance,as well as excessive Tau protein phosphorylation.This paper provides a comprehensive review of recent domestic and international literature on the interplay between autophagy and characteristic neuropathological changes observed in AD,elucidates the regulatory mechanisms of autophagy-related signaling pathways implicated in AD pathology,explores correlation studies on traditional Chinese medicine treatments targeting“phlegm turbidness”,aiming to offer novel research directions and therapeutic targets for clinical advancements in AD through modulation of autophagy.
作者
王语晴
刘欣欣
姜玲
王杨
侯志涛
宋晓晨
胡新颖
陈晶
WANG Yuqing;LIU Xinxin;JANG Ling;WANG Yang;HOU Zhitao;SONG Xiaochen;HU Xinying;CHEN Jing(Heilongjiang University of Chinese Medicine,Harbin 150040,Heilongjiang,China)
出处
《辽宁中医药大学学报》
CAS
2024年第3期32-37,共6页
Journal of Liaoning University of Traditional Chinese Medicine
基金
国家自然科学基金项目(82274395)
黑龙江省省属本科高校改革发展资金项目。
