Mechanisms and Therapeutic Targeting of the cGAS-STING Pathway in Central Nervous System Disorders.
Mechanisms and Therapeutic Targeting of the cGAS-STING Pathway in Central Nervous System Disorders.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Nanjing, CN · Author affiliation
Department of Neurology, Nanjing Drum Tower Hospital, Joint Institute of Nanjing Drum Tower Hospital for Life and Health, College of Life Science, Nanjing Normal University, Nanjing 210008, China.Location evidence
A plain-language reading has not been prepared for this paper yet.
Original abstract
OBJECTIVE: The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is a core DNA-sensing axis in innate immunity and has been increasingly implicated in the pathogenesis of multiple Central Nervous System (CNS) disorders. This review summarizes current knowledge of cGAS-STING signaling in CNS disorders and evaluates its therapeutic potential. METHODS: Relevant studies on cGAS-STING signaling in CNS disorders were collected from PubMed and Web of Science, with emphasis on disease mechanisms, neuroinflammatory regulation, and pathway-targeted therapeutic strategies. RESULTS: In the CNS, cGAS-STING signaling exhibits marked region-, cell-, and pathology-dependent heterogeneity. Aberrant DNA sensing activates this pathway and amplifies neuroinflammation, cellular stress, and tissue injury in Alzheimer's Disease (AD), Parkinson's Disease (PD), Amyotrophic Lateral Sclerosis (ALS), ataxia-telangiectasia (A-T), and ischemic and hemorrhagic stroke. Pharmacological inhibition of cGAS, cyclic GMP-AMP (cGAMP), or STING, together with emerging delivery strategies, has shown promise in preclinical models. DISCUSSION: Clinical translation remains limited by incomplete validation of pathway specificity, limited human evidence, restricted brain delivery, and inconsistent efficacy assessment. CONCLUSION: The cGAS-STING pathway links aberrant DNA sensing to innate immune activation and CNS pathology. Clarifying its disease-, cell-, and stage-specific roles may support future targeted therapeutic strategies for CNS disorders.