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

• Published in: Neural regeneration research Vol. 20; no. 8; pp. 2361 - 2372
• Main Authors: Zhou, Shengyang, Li, Ting, Zhang, Wei, Wu, Jian, Hong, Hui, Quan, Wei, Qiao, Xinyu, Cui, Chun, Qiao, Chenmeng, Zhao, Weijiang, Shen, Yanqin
• Format: Journal Article
• Language: English
• Published: India Medknow Publications & Media Pvt. Ltd 01.08.2025; Laboratory of Neurodegenerative and Neuroinjury Diseases,Wuxi Medicine School,Jiangnan University,Wuxi,Jiangsu Province,China; Wolters Kluwer - Medknow; Wolters Kluwer Medknow Publications
• Subjects: Adenosine; cyclic guanosine monophosphate adenosine monophosphate synthase; h151; Interferon; interferon regulatory factor 7; m1 phenotype; neurodegenerative disease; neuroinflammation; Parkinson's disease; ru521; sting; type i interferon; cyclic guanosine monophosphate adenosine monophosphate synthase; neurodegenerative disease; Parkinson's disease; H151; neuroinflammation; type Ⅰ interferon; M1 phenotype; STING; RU521; interferon regulatory factor 7
• ISSN: 1673-5374; 1876-7958
• DOI: 10.4103/NRR.NRR-D-23-01684

JOURNAL/nrgr/04.03/01300535-202508000-00026/figure1/v/2024-09-30T120553Z/r/image-tiff 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, siRNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase, tumor necrosis factor α, 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