中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (8): 2361-2372.doi: 10.4103/NRR.NRR-D-23-01684

• 原著:退行性病与再生 • 上一篇    下一篇

调控cGAS-STING-干扰素调节因子 7通路对帕金森病神经炎症的影响

  

  • 出版日期:2025-08-15 发布日期:2024-12-14

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

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

  1. Laboratory of Neurodegenerative and Neuroinjury Diseases, Wuxi Medicine School, Jiangnan University, Wuxi, Jiangsu Province, China
  • Online:2025-08-15 Published:2024-12-14
  • Contact: Weijiang Zhao, PhD, weijiangzhao@jiangnan.edu.cn; Yanqin Shen, PhD, shenyanqin@jiangnan.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 82171429, 81771384 and a grant from Wuxi Municipal Health Commission, No. 1286010241190480 (all to YS).

摘要:

干扰素调节因子7对免疫反应十分重要。然而,先天免疫中干扰素调节因子7介导的信号通路是否会导致帕金森病仍不得而知。此次实验首先发现MPTP诱导建立的帕金森病小鼠模型中干扰素调节因子 7水平明显上调,且与小胶质细胞的共定位。继而以选择性cGAS抑制剂RU.521和STING抑制剂H151干预MPP+诱导BV2小胶质细胞,干扰素调节因子7的活化都受到了抑制,且BV2细胞向神经毒性M1表型的转化也受到抑制。最后以小干扰RNA抑制BV2小胶质细胞中IRF7的表达,可见炎症蛋白诱导型一氧化氮合酶、肿瘤坏死因子α、CD16、CD32和CD86表达受到减少,抗炎标志物ARG1和YM1表达增加。结果表明,cGAS-STING-干扰素调节因子 7通路可在帕金森病发病中发挥重要作用。

https://orcid.org/0000-0003-1724-4135 (Yanqin Shen)

关键词: 干扰素调节因子7,  cGAS,  STING,  帕金森病,  神经退行性疾病,  H151,  RU.521,  神经炎症,  M1表型,  I型干扰素

Abstract: 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

Key words: cyclic guanosine monophosphate adenosine monophosphate synthase,  H151,  interferon regulatory factor 7,  M1 phenotype,   neurodegenerative disease,  neuroinflammation,  Parkinson’s disease,  RU521,  STING,  type I interferon