摘要
天然免疫激活在阿尔茨海默病(Alzheimer disease,AD)的发病机制中发挥着关键作用。AD是一种进行性神经退行性疾病,其主要病理特征为老年斑和神经原纤维缠结。近年研究表明,胞质DNA感应通路——由环状GMP-AMP合成酶(cyclic GMP-AMP synthase,GAS)/干扰素基因刺激蛋白(stimulator of interferon genes,STING)介导的通路——已成为AD病理进程中的关键调控枢纽。然而,cGAS-STING通路激活诱发AD的具体分子机制仍有待阐明。本文概述cGAS-STING信号通路的分子机制及其在AD脑内的细胞类型特异性激活模式,介绍该通路活化参与AD病理进程的多重作用机制,以及整合调控该通路的上游信号网络。
Innate immune activation plays a central role in the pathogenesis of Alzheimer disease(AD),a progressive neurodegenerative disorder characterized by the accumulation of senile plaques and neurofibrillary tangles.Emerging evidence has highlighted the cytoplasmic DNA-sensing pathway,particularly the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)axis,as a critical regulatory hub in AD pathology.However,the precise molecular mechanisms through which cGAS-STING activation drives disease progression remain incompletely understood.We first outlins the molecular mechanisms of the cGAS-STING signaling pathway and its cell-type-specific activation patterns in the AD brain.We then delineate the multifaceted mechanisms by which this pathway contributes to AD pathogenesis.Finally,the review integrates current understanding of the upstream signaling networks that regulate cGAS-STING activity.
作者
王智慧
李强
WANG Zhihui;LI Qiang(Department of Neurology,The Affiliated Hospital of Chifeng University,Chifeng 024005,China)
出处
《中国病理生理杂志》
北大核心
2026年第2期395-400,共6页
Chinese Journal of Pathophysiology
基金
内蒙古自然科学基金资助项目(No.2022MS08046)
赤峰市自然科学基金资助项目(No.SZR2023053)
内蒙古人类遗传病研究自治区高等学校重点实验室开放课题(No.YC202305,No.YC202304)。
