作者
John V Pluvinage, Michael S Haney, Benjamin AH Smith, Jerry Sun, Tal Iram, Liana Bonanno, Lulin Li, Davis P Lee, David W Morgens, Andrew C Yang, Steven R Shuken, David Gate, Madeleine Scott, Purvesh Khatri, Jian Luo, Carolyn R Bertozzi, Michael C Bassik, Tony Wyss-Coray
发表日期
2019/4/11
期刊
Nature
卷号
568
期号
7751
页码范围
187-192
出版商
Nature Publishing Group UK
简介
Microglia maintain homeostasis in the central nervous system through phagocytic clearance of protein aggregates and cellular debris. This function deteriorates during ageing and neurodegenerative disease, concomitant with cognitive decline. However, the mechanisms of impaired microglial homeostatic function and the cognitive effects of restoring this function remain unknown. We combined CRISPR–Cas9 knockout screens with RNA sequencing analysis to discover age-related genetic modifiers of microglial phagocytosis. These screens identified CD22, a canonical B cell receptor, as a negative regulator of phagocytosis that is upregulated on aged microglia. CD22 mediates the anti-phagocytic effect of α2,6-linked sialic acid, and inhibition of CD22 promotes the clearance of myelin debris, amyloid-β oligomers and α-synuclein fibrils in vivo. Long-term central nervous system delivery of an antibody that blocks …
学术搜索中的文章
JV Pluvinage, MS Haney, BAH Smith, J Sun, T Iram… - Nature, 2019