ChK1 activation induces reactive astrogliosis through CIP2A/PP2A/STAT3 pathway in Alzheimer's disease.
ChK1 activation induces reactive astrogliosis through CIP2A/PP2A/STAT3 pathway in Alzheimer's disease.
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在阿尔茨海默病中，ChK1 激活通过 CIP2A/PP2A/STAT3 通路诱导反应性星形胶质细胞增生。
DOI：
10.1096/fj.202101625r
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Xiaoch
中科院分区：
文献类型：
--
作者：
Ying Zhou;Xiaoyuan Liu;Shuqing Ma;Nan Zhang;Dichen Yang;Ling Wang;Simin Ye;Qiongying Zhang;Jing Ruan;Jun Ma;Shiyi Wang;Nan Jiang;Zongyuan Zhao;Shujue Zhao;Chenfei Zheng;Xiaofang Fan;Yongsheng Gong;Mahaman Yacoubou Abdoul Razak;Wenting Hu;Jingye Pan;Xiaoch
Cancerous Inhibitor of PP2A (CIP2A), an endogenous PP2A inhibitor, is upregulated and causes reactive astrogliosis, synaptic degeneration, and cognitive deficits in Alzheimer's disease (AD). However, the mechanism underlying the increased CIP2A expression in AD brains remains unclear. We here demonstrated that the DNA damage-related Checkpoint kinase 1 (ChK1) is activated in AD human brains and 3xTg-AD mice. ChK1-mediated CIP2A overexpression drives inhibition of PP2A and activates STAT3, then leads to reactive astrogliosis and neurodegeneration in vitro. Infection of mouse brain with GFAP-ChK1-AAV induced AD-like cognitive deficits and exacerbated AD pathologies in vivo. In conclusion, we showed that ChK1 activation induces reactive astrogliosis, degeneration of neurons, and exacerbation of AD through the CIP2A-PP2A-STAT3 pathway, and inhibiting ChK1may be a potential therapeutic approach for AD treatment.
