Complement component (3b/4b) receptor 1 (CR1) expression is positively related to the abundance of phosphorylated microtubule-associated protein tau (tau), and CR1 expression is associated with susceptibility to Alzheimer's disease. However, the exact role of CR1 in tau protein-associated neurodegenerative diseases is unknown. In this study, we show that the mouse Cr1-related protein Y (Crry) gene, Crry, is localized to microglia. We also found that Crry protein expression in the hippocampus and cortex was significantly elevated in P301S mice (a mouse model widely used for investigating tau pathology) compared with that in wild-type mice. Tau protein phosphorylation (at serine 202, threonine 205, threonine 231, and serine 262) and expression of the major tau kinases glycogen synthase kinase-3 beta and cyclin-dependent-like kinase 5 were greater in P301S mice than in wild-type mice. Crry silencing by lentivirus-transfected short hairpin RNA led to greatly reduced tau phosphorylation and glycogen synthase kinase-3 beta and cyclin-dependent-like kinase 5 activity. Crry silencing reduced neuronal apoptosis and rescued cognitive impairment of P301S mice. Crry silencing also reduced the levels of the neuroinflammatory factors interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 and the complement components complement 3 and complement component 3b. Our results suggest that Crry silencing in the P301S mouse model reduces tau protein phosphorylation by reducing the levels of neuroinflammation and complement components, thereby improving cognitive function.

Xi-Chen Zhu;Lu Liu;Wen-Zhuo Dai;Tao Ma

Department of Neurology,Wuxi No.2 People's Hospital of Nanjing Medical University,Wuxi,Jiangsu Province,China;Department of Neurology,Wuxi No.2 People's Hospital,Affiliated Wuxi Clinical College of Nantong University,Wuxi,Jiangsu Province,China

中国神经再生研究（英文版）

[1]Xi-Chen Zhu;Lu Liu;Wen-Zhuo Dai;Tao Ma-.Crry silencing alleviates Alzheimer 's disease injury by regulating neuroinflammatory cytokines and the complement system)[J].中国神经再生研究（英文版）,2022(08):1841-1849

Crry,P301S

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