Translational Medicine Center of Pain, Emotion and Cognition, Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, Ningbo 315211, China.
State Key Laboratory of Microbial Metabolism, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Int Immunopharmacol. 2021 Dec;101(Pt A):108263. doi: 10.1016/j.intimp.2021.108263. Epub 2021 Oct 29.
Both the total amount and annual growth rate of Alzheimer's disease (AD) patients in China are much higher than in other regions in the world. This trend of rapid growth will be difficult to change in the next few decades, hence the prevention and treatment situation of AD patients in China is more severe. Maintaining the balance between the production and removal pathways of Aβ is an important guarantee for the body to maintain its normal physiological state. The dysfunction of Aβ clearance is an important factor of Aβ accumulation in brain tissue of AD patients causing neurotoxicity of synaptic damage and neuronal death. Based on the literature review, it introduced the important role of microglias in clearing Aβ deposits in the process of Alzheimer's disease. And most of these phagocytic cells were the specific phenotype of disease-related microglia (DAM-I/DAM-II) that induced microglial differentiation after activation. IL-10KO promoted the transformation of microglial phenotype DAM-II, and enhanced its phagocytosis for Aβ oligomers. There is a hypothesis that IL-10R/STAT3 negatively regulates microglial phagocytosis. It was learnt that blocking the IL-10R/STAT3 pathway promoted microglial activation and enhanced phagocytosis. The comprehensive review on the involvement of IL-10R/STAT3 pathway in the process of AD would open up new ideas and discover new targets for the development of new therapeutic drugs.
中国的阿尔茨海默病（AD）患者人数和年增长率均远高于世界其他地区。这种快速增长的趋势在未来几十年内很难改变，因此中国 AD 患者的防治形势更加严峻。维持 Aβ产生和清除途径之间的平衡是维持机体正常生理状态的重要保障。Aβ清除功能障碍是 AD 患者脑组织中 Aβ蓄积导致突触损伤和神经元死亡的神经毒性的重要因素。基于文献综述，介绍了小胶质细胞在清除 AD 过程中 Aβ沉积中的重要作用。而这些吞噬细胞大多是激活后诱导小胶质细胞分化的疾病相关小胶质细胞（DAM-I/DAM-II）的特定表型。IL-10KO 促进小胶质细胞表型 DAM-II 的转化，并增强其对 Aβ寡聚物的吞噬作用。有假说认为，IL-10R/STAT3 负调节小胶质细胞的吞噬作用。研究发现，阻断 IL-10R/STAT3 通路可促进小胶质细胞的激活和吞噬作用。对 IL-10R/STAT3 通路在 AD 发病机制中的作用进行综合综述，可为开发新的治疗药物开辟新思路，发现新的靶点。
