中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (8): 3285-3300.doi: 10.4103/NRR.NRR-D-25-00367

• 综述:神经损伤修复保护与再生 •    下一篇

cGAS-STING轴：神经系统稳态和神经炎症发生的中枢调节器

  

  • 出版日期:2026-08-18 发布日期:2026-04-23

cGAS-STING axis: A central regulator of central nervous system homeostasis and neuroinflammatory pathogenesis

Jiajie Zhang1, 2, #, Jiarui Li1, #, Yanan Li3, Chunxiao Liu3, Lei Shi2, Yuxuan Qian4, *, Qian Chen4, *, Qi Zhang2, *   

  1. 1Graduate School of Hebei Medical University, Shijiazhuang, Hebei Province, China; 
    2Department of Anesthesiology, Hebei Children’s Hospital, Shijiazhuang, Hebei Province, China; 
    3Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China; 
    4Department of Orthopedic Surgery, Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • Online:2026-08-18 Published:2026-04-23
  • Contact: Qi Zhang, PhD, 90100101@hebmu.edu.cn; Qian Chen, MD, qian_chen15@fudan.edu.cn; Yuxuan Qian, MD, yx.qian@foxmail.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 82301382; the Natural Science Foundation of Hebei Province, No. H2022316001; Government Funded Clinical Medicine Excellent Talents Project, No. ZF2023126, and the Postdoctoral Research Support Program for Clinical Medicine of Hebei Medical University, No. PD2023004 (all to QZ).

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摘要：

越来越多的证据表明，环鸟苷单磷酸-腺苷单磷酸合酶（cGAS）和干扰素基因刺激因子（STING）诱导的I型干扰素反应过程与健康和神经炎症疾病密切相关。cGAS-STING轴的异常激活或失控会影响神经炎症的发展。因此，此次综述比较了其在主要神经系统疾病（创伤性脑损伤、阿尔茨海默病、帕金森病、亨廷顿病、多发性硬化、单纯疱疹性脑炎、共济失调毛细血管扩张）中的作用机制。此外，cGAS-STING轴在调节神经炎症和靶向干预相关疾病方面已成为当前临床研究的热点。文章还介绍了一系列针对cGAS-STING轴的cGAS抑制剂和小分子抑制剂的迭代和发展，并展望了STING抑制剂和激动剂在临床研究中的应用前景。总之，cGAS-STING轴对神经系统疾病的影响可能比单个蛋白质或基因更大。未来应侧重于阐明该轴的功能动力学和调控网络，描绘其与其他信号级联的串扰。这将提供机制上为相关疾病制定有针对性的治疗策略，并可能促进药物在不同疾病背景下的再利用。


https://orcid.org/0000-0003-0727-1607 (Qi Zhang); https://orcid.org/0000-0001-9913-0750 (Qian Chen); 

https://orcid.org/0000-0002-0164-732X (Yuxuan Qian)

关键词: 星形胶质细胞, cGAS-STING轴, 小胶质细胞, 线粒体DNA, 神经变性, 神经免疫学, 神经炎症, 神经系统疾病, NLRP3, 小分子抑制剂, I型干扰素

Abstract: An increasing amount of evidence shows that type I interferon response, which is induced by cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) and stimulator of interferon genes (STING) is closely associated with health and neuroinflammatory diseases. Abnormal activation or loss of control of the cGAS-STING axis affects the development of neuroinflammation. Thus, we examined its role in major neurological diseases, including traumatic brain injury, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, multiple sclerosis, herpes simplex encephalitis, and ataxia-telangiectasia. Additionally, targeted intervention of the cGAS-STING axis to control neuroinflammation and treat related diseases has become the focus of current clinical research. This article describes the development of cGAS inhibitors and small molecules that target the cGAS-STING axis and explores the potential applications of STING inhibitors and agonists in clinical research. In summary, the cGAS-STING axis may impact neurological diseases more than a single protein or gene. Future studies should focus on elucidating the functional dynamics and regulatory networks of this axis and delineating its crosstalk with other signaling cascades. These investigations will provide mechanistic insights for developing targeted therapeutic strategies for associated disorders and potentially facilitate drug repurposing across diverse disease contexts. 

Key words: astrocytes, cGAS-STING axis, microglia, mitochondrial DNA, neurodegeneration, neuroimmunology, neuroinflammation, neurological disorders, NLRP3, small molecule inhibitors, type I interferon