Zhao Wenhui, Liu Zhongxuan, Wu Jiannan, Liu Anran, Yan Junqiang
Neuromolecular Biology Laboratory, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan Province, China.
Department of Rehabilitation, The First People's Hospital of Zhengzhou, Zhengzhou, Henan Province.
Neural Regen Res. 2026 Apr 1;21(4):1497-1511. doi: 10.4103/NRR.NRR-D-24-01343. Epub 2025 Mar 25.
For diverse neurodegenerative disorders, microglial cells are activated. Furthermore, dysfunctional and hyperactivated microglia initiate mitochondrial autophagy, oxidative stress, and pathological protein accumulation, ending with neuroinflammation that exacerbates damage to dopaminergic neurons and contributes significantly to the pathology of neurodegenerative disorder. Microglial over-activation is closely associated with the secretion of pro-inflammatory cytokines, the phagocytosis of injured neurons, and the modulation of neurotoxic environments. This review summarizes the role of microglia neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, multiple system atrophy, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, cortical degeneration, Lewy body dementia, and Huntington's disease. It also discusses novel forms of cell death such as ferroptosis, cuproptosis, disulfidptosis, and parthanatos (poly(adenosine diphosphate ribose) polymerase 1-dependent cell death), as well as the impact of regulatory factors related to microglial inflammation on microglial activation and neuroinflammation. The aim is to identify potential targets for microglial cell therapy in neurodegenerative diseases.
在多种神经退行性疾病中，小胶质细胞会被激活。此外，功能失调和过度激活的小胶质细胞会引发线粒体自噬、氧化应激和病理性蛋白质积累，最终导致神经炎症，加重对多巴胺能神经元的损伤，并在神经退行性疾病的病理过程中起重要作用。小胶质细胞过度激活与促炎细胞因子的分泌、受损神经元的吞噬作用以及神经毒性环境的调节密切相关。本综述总结了小胶质细胞在神经退行性疾病中的作用，如阿尔茨海默病、帕金森病、多发性硬化症、多系统萎缩、肌萎缩侧索硬化症、额颞叶痴呆、进行性核上性麻痹、皮质变性、路易体痴呆和亨廷顿舞蹈病。还讨论了新的细胞死亡形式，如铁死亡、铜死亡、二硫化物死亡和PARP1依赖性细胞死亡（parthanatos），以及与小胶质细胞炎症相关的调节因子对小胶质细胞激活和神经炎症的影响。目的是确定神经退行性疾病中小胶质细胞治疗的潜在靶点。
