文献类型：期刊文献

英文题名：Microglial immunometabolic reprogramming in Alzheimer's disease: From mitochondrial dysfunction and redox imbalance to NLRP3 inflammasome-driven neuroinflammation

作者：Li, Siyu[1];Jin, Juntao[1];Liu, Yingying[1];Yuan, Jing[1];Dong, Yuhan[1];Wang, Ziyi[1];Li, Lu[1];Zhang, Yamin[1,2]

第一作者：Li, Siyu

通信作者：Zhang, YM[1]

机构：[1]Gansu Univ Chinese Med, Clin Med Coll 1, Lanzhou, Gansu, Peoples R China;[2]Gansu Prov Hosp, Dept Neurol, Lanzhou 730000, Gansu, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Prov Hosp, Dept Neurol, Lanzhou 730000, Gansu, Peoples R China.

年份：2026

外文期刊名：JOURNAL OF ALZHEIMERS DISEASE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001837764400001)】；

基金：The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Gansu provincial joint research fund of science and technology planning project (Grant No. 24JRRA890) and the Second-Year Research Start-up Fund for the Talent Pool of Gansu Provincial Hospital (Grant No. 2026KYQDJ-B-45).

语种：英文

外文关键词：Alzheimer's disease; immunometabolic reprogramming; microglia; mitochondrial dysfunction; neuroinflammation; NLRP3 inflammasome; redox imbalance

摘要：Alzheimer's disease (AD) is increasingly recognized as a disorder in which amyloid-beta deposition and tau pathology interact with neuroinflammation and metabolic dysregulation. Although mitochondrial dysfunction, redox imbalance, and NLRP3 inflammasome activation have each been implicated in AD pathogenesis, their mechanistic continuity within microglial immunometabolic reprogramming remains insufficiently defined. This narrative review integrates mechanistic, preclinical, and human-relevant evidence to propose a stage-dependent mitochondrial dysfunction-redox imbalance-NLRP3 inflammasome axis. We discuss how AD-related stimuli shift microglia toward a pro-inflammatory metabolic phenotype; how impaired mitochondrial quality control promotes reactive oxygen species generation and oxidized mitochondrial DNA release; and how these signals facilitate NLRP3 inflammasome activation and sustained inflammatory amplification. We further summarize therapeutic strategies targeting upstream mitochondrial homeostasis, intermediate metabolic-redox coupling, and downstream NLRP3 signaling, while emphasizing the translational limitations and biomarker needs. We conclude that this proposed axis provides a testable stage-dependent framework for interpreting chronic, self-amplifying neuroinflammation in AD and may inform biomarker-guided, combinatorial therapeutic strategies.