Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (9): 4028-4044.doi: 10.4103/NRR.NRR-D-24-01516

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cGAS–STING pathway modulation: A new hope for neural regeneration

Jinghan Zhang1, #, Mouyuan Sun2, *, #, Yaxian Luo2, Mikko Petteri Räisänen3, Lianjie Peng2, Luying Qin2, Mengfei Yu2, *, Haifei Shi1, *   

  1. 1Department of Orthopedics, the First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China;
    2Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, Zhejiang Province, China; 
    3Department of Orthopedics, Traumatology, and Hand Surgery, Kuopio University Hospital, Kuopio, Finland
  • Online:2026-09-15 Published:2026-05-16
  • Contact: Haifei Shi, MD, shihaifei@zju.edu.cn; Mengfei Yu, MD, yumengfei@zju.edu.cn; Mouyuan Sun, MD, sunmouyuan777@zju.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 82272465 (to HS), 82122014 (to MY), 82071085 (to MY); National Key Research and Development Program of China, No. 2023YFB3813003 (to MY); the Natural Science Foundation of Zhejiang Province of China, No. LQN25H140004 (to MY); and China Postdoctoral Science Foundation, Nos. 2024T170782 (to MY), 2023M743009 (to MY).

Abstract: In recent decades, the limitations of therapeutic interventions have elevated neurological disorders and injuries to a prominent position in academic research. Existing neurotherapeutic methodologies have demonstrated insufficient efficacy in fostering neural regeneration. The current integration of precision medicine technologies and innovative tissue engineering methods holds significant promise for attaining neural regeneration. The cGAS–STING pathway, a pivotal component of the innate immune system, plays a crucial role in the pathological processes of various neurological diseases and injuries. In neuroinflammatory diseases and neural injuries, aberrant activation of the cGAS–STING pathway amplifies neuroinflammation, type I interferon responses, and cell death. Inhibition of cGAS–STING-related genes holds promise for promoting neural regeneration following disease recovery and defect regeneration. In this review, the foundational pathophysiological mechanisms underlying cGAS–STING-related gene regulation in neurological disorders and injuries are elucidated with a special emphasis on its implications in nerve-related cells. In this review, we highlight the advances in tissue engineering technologies that integrate cGAS–STING pathway modulators, highlighting their potential therapeutic efficacy in modulating neural regeneration. Nevertheless, the role of the cGAS–STING pathway in neural regeneration remains relatively limited. Bibliometric analysis demonstrates a significant correlation of cGAS–STING pathway activation with various neuropathological processes. Studies have progressively focused on the critical role of this pathway in neurological diseases and injuries. As it stands, the effectiveness of tissue engineering technologies involving cGAS–STING-related gene modulators in achieving neural regeneration remains unfulfilled in its potential. Future research must apply advanced omics technologies to further delineate the exact functions of the cGAS–STING pathway in neural regeneration. Integration of these results with precision medicine approaches will be necessary for creating tissue engineering biomaterials with capabilities for precise delivery and targeted controlled release of cGAS–STING-related genes in neural regeneration-related cells, towards functional recovery from neurological injury and diseases.

Key words: biomaterials, cGAS–STING, nerve injury, neural regeneration, neurodegeneration, neuroinflammation, precision medicine, tissue engineering