小胶质细胞代谢重编程在阿尔茨海默病中的作用研究进展^*

Microglial metabolic reprogramming in Alzheimer disease: emerging mechanisms and therapeutic perspectives

摘要

阿尔茨海默病(AD)是一种以认知功能持续退化为主要特征的中枢神经系统退行性疾病,严重威胁全球老龄人口的健康。尽管β淀粉样蛋白沉积、tau蛋白异常磷酸化等经典病理机制已被广泛研究,但近年来越来越多的证据表明,脑内固有免疫细胞——小胶质细胞的代谢重编程在AD的发生与进展中发挥着核心调控作用。小胶质细胞葡萄糖、脂质、氨基酸等代谢途径的紊乱,不仅驱动其促炎/抗炎表型的动态转化,还通过调控神经炎症、吞噬功能及细胞间信号网络,影响AD的病理级联反应。该文系统综述了小胶质细胞代谢重编程在AD发病中的作用,旨在为AD的精准防治提供新的理论靶点。

Abstract

Alzheimer disease (AD) is a neurodegenerative disorder of the central nervous system, chiefly marked by a progressive deterioration of cognitive function, significantly jeopardizing the health of the global aged population. Despite extensive research on classical pathological mechanisms like Aβ deposition and abnormal tau protein phosphorylation, recent evidence suggests that the metabolic reprogramming of microglia—innate immune cells in the brain plays a fundamental regulatory role in the onset and advancement of AD. The dysregulation of microglial metabolic pathways, encompassing glucose, lipid, and amino acid metabolism, not only facilitates the dynamic shift between pro-inflammatory and anti-inflammatory phenotypes but also significantly influences the pathological progression of AD by modulating neuroinflammation, phagocytic activity, and intercellular signaling networks. This review carefully examines the role of microglial metabolic reprogramming in the etiology of AD, with the objective of offering novel theoretical targets for precise prevention and therapy of the condition.

关键词

阿尔茨海默病 / 小胶质细胞 / 代谢重编程 / 神经炎症

Key words

Alzheimer disease / Microglia / Metabolic reprogramming / Neuroinflammation