The cytosolic DNA‐sensing cGASSTING pathway in neurodegenerative diseases

Author:

Guo Xiaofeng12ORCID,Yang Lin1ORCID,Wang Jiawei1ORCID,Wu You1ORCID,Li Yi1ORCID,Du Lixia1ORCID,Li Ling1ORCID,Fang Zongping134ORCID,Zhang Xijing1ORCID

Affiliation:

1. Department of Critical Care Medicine, Xijing Hospital The Fourth Military Medical University China

2. Department of Intensive Care Unit Joint Logistics Force No. 988 Hospital Zhengzhou China

3. Department of Anesthesiology, Xijing Hospital Fourth Military Medical University Shaanxi China

4. Translational Research Institute of Brain and Brain‐Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine Tongji University Shanghai China

Abstract

AbstractBackgroundWith the widespread prevalence of neurodegenerative diseases (NDs) and high rates of mortality and disability, it is imminent to find accurate targets for intervention. There is growing evidence that neuroimmunity is pivotal in the pathology of NDs and that interventions targeting neuroimmunity hold great promise. Exogenous or dislocated nucleic acids activate the cytosolic DNA sensor cyclic GMP‐AMP synthase (cGAS), activating the stimulator of interferon genes (STING). The activated STING triggers innate immune responses and then the cGAS‐STING signaling pathway links abnormal nucleic acid sensing to the immune response. Recently, numerous studies have shown that neuroinflammation regulated by cGAS‐STING signaling plays an essential role in NDs.AimsIn this review, we summarized the mechanism of cGAS‐STING signaling in NDs and focused on inhibitors targeting cGAS‐STING.ConclusionThe cGAS‐STING signaling plays an important role in the pathogenesis of NDs. Inhibiting the cGAS‐STING signaling may provide new measures in the treatment of NDs.

Funder

National Natural Science Foundation of China

Publisher

Wiley

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