REVIEW article
Front. Aging Neurosci.
Sec. Cellular and Molecular Mechanisms of Brain-aging
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1659216
STING-mediated Neuroinflammation: A Therapeutic Target in Neurodegenerative Diseases
Provisionally accepted
Haoqin Zhang1,2
Ziyang He1,2
Can Yin1Shiyi Yang1Jianqiao Li1Hong Lin1
Guishan Hu1
Anguo Wu1,2
Dalian Qin1,2Guangqiang Hu1*
Lu Yu1,2*- 1Southwest Medical University, Luzhou, China
- 2Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou, China
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The stimulator of interferon genes (STING) plays a crucial role as an adaptor in innate immune defense, orchestrating key inflammatory processes through the modulation of type I interferon signaling and activation of cytokine networks. Recent studies have identified STING-induced neuroinflammatory responses as a major factor in the progression of neurological diseases, particularly in neurodegenerative disorders. This review methodically explores the structural basis of STING activation and its role in driving pathological inflammation. And the classic and non-classic pathways of STING as well as their roles in neurodegenerative diseases were discussed. Additionally, it critically assesses new pharmacological approaches that target the STING pathway, emphasizing anti-inflammatory treatments ranging from synthetic small-molecule inhibitors to bioactive compounds sourced from traditional Chinese medicines, which aim to mitigate neurotoxic inflammation. By combining mechanistic insights with therapeutic advancements, this paper presents an innovative transformation framework aimed at developing anti-inflammatory therapies targeting the STING pathway to treat neurodegenerative diseases. The core contribution of this framework lies in systematically bridging the innate immune regulation and neuroinflammation control mechanisms, providing a new strategy for disease intervention.
Keywords: Stimulator of interferon genes, Neuroinflammation, Neurodegenerative Diseases, cGAS-STING signal pathway, modulators, therapeutic strategies
Received: 04 Jul 2025; Accepted: 01 Sep 2025.
Copyright: © 2025 Zhang, He, Yin, Yang, Li, Lin, Hu, Wu, Qin, Hu and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Guangqiang Hu, Southwest Medical University, Luzhou, China
Lu Yu, Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou, China
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