Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Kyushu University Institute for Advanced Study, Fukuoka 819-0395, Japan.
Cells. 2023 Apr 21;12(8):1207. doi: 10.3390/cells12081207.
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease worldwide, but therapeutic strategies to slow down AD pathology and symptoms have not yet been successful. While attention has been focused on neurodegeneration in AD pathogenesis, recent decades have provided evidence of the importance of microglia, and resident immune cells in the central nervous system. In addition, new technologies, including single-cell RNA sequencing, have revealed heterogeneous cell states of microglia in AD. In this review, we systematically summarize the microglial response to amyloid-β and tau tangles, and the risk factor genes expressed in microglia. Furthermore, we discuss the characteristics of protective microglia that appear during AD pathology and the relationship between AD and microglia-induced inflammation during chronic pain. Understanding the diverse roles of microglia will help identify new therapeutic strategies for AD.
阿尔茨海默病（AD）是全球最常见的神经退行性疾病，但减缓 AD 病理和症状的治疗策略尚未成功。虽然人们一直关注 AD 发病机制中的神经退行性变，但近几十年来的研究证据表明小胶质细胞（中枢神经系统中的常驻免疫细胞）的重要性。此外，单细胞 RNA 测序等新技术揭示了 AD 中小胶质细胞的异质细胞状态。在这篇综述中，我们系统地总结了小胶质细胞对淀粉样蛋白-β和 tau 缠结的反应，以及小胶质细胞中表达的风险因子基因。此外，我们讨论了在 AD 病理过程中出现的保护性小胶质细胞的特征，以及 AD 与慢性疼痛中小胶质细胞诱导的炎症之间的关系。了解小胶质细胞的多种作用将有助于为 AD 确定新的治疗策略。
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