神经炎症
小胶质细胞
条件基因敲除
基因剔除小鼠
炎症
神经退行性变
医学
神经科学
免疫学
生物
促炎细胞因子
阿尔茨海默病
病理
疾病
受体
内科学
表型
基因
生物化学
作者
Jinbo Cheng,Yuan Dong,Jun Ma,Rui‐Yuan Pan,Yuhe Liao,Xu Kong,Xiaoheng Li,Shuoshuo Li,Ping-Fang Chen,Liang Wang,Ye Yu,Zengqiang Yuan
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2021-08-27
卷期号:7 (35)
被引量:53
标识
DOI:10.1126/sciadv.abe3600
摘要
Alzheimer's disease (AD) is the most common neurodegenerative disease in the world. Neuronal calcium dysfunction and microglial-mediated neuroinflammation are closely associated with the development of AD. However, it remains unknown whether calcium dysfunction contributes to microglial activation and, in turn, AD pathology in vivo. In this study, we demonstrated that the expression of calcium homeostasis modulator family protein 2 (Calhm2) is increased in an AD mouse model. In 5×FAD mice carrying five familial AD gene mutations, both conventional knockout of Calhm2 and conditional microglial knockout of Calhm2 significantly reduced amyloid β deposition, neuroinflammation, and cognitive impairments. Mechanistically, knockout of Calhm2 inhibited microglial proinflammatory activity but increased phagocytic activity, leading to restoration of the balance between inflammation and phagocytosis. In addition, knockout of Calhm2 reduced acute LPS-induced neuroinflammation. These results highlight an important role for Calhm2 in microglial activation and provide a potential therapeutic target for diseases related to microglia-mediated neuroinflammation.
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