The cGAS-STING-interferon regulatory factor 7 pathway regulates neuroinflammation in Parkinson's disease  

作　　者：Shengyang Zhou Ting Li Wei Zhang Jian Wu Hui Hong Wei Quan Xinyu Qiao Chun Cui Chenmeng Qiao Weijiang Zhao Yanqin Shen 

机构地区：[1]Laboratory of Neurodegenerative and Neuroinjury Diseases,Wuxi Medicine School,Jiangnan University,Wuxi,Jiangsu Province,China

出　　处：《Neural Regeneration Research》2025年第8期2361-2372,共12页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,Nos.82171429,81771384;a grant from Wuxi Municipal Health Commission,No.1286010241190480(all to YS)。

摘　　要：Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.

关 键 词：cyclic guanosine monophosphate adenosine monophosphate synthase H151 interferon regulatory factor 7 M1 phenotype neurodegenerative disease NEUROINFLAMMATION Parkinson’s disease RU521 STING type I interferon 

分 类 号：R742.5[医药卫生—神经病学与精神病学]