[Mechanisms of cGAS-STING signaling pathway mediated neuroinflammation in central nervous system and their therapeutic implications].

The cGAS-STING signaling pathway is a crucial mechanism by which cells sense aberrant DNA and trigger type Ⅰ interferon and inflammatory responses. Emerging evidence indicates that in various central nervous system (CNS) diseases, events such as mitochondrial damage, release of mitochondrial DNA, nuclear DNA damage, lysosomal rupture, and cell death-associated DNA leakage can activate cGAS-STING signaling pathway in microglia, astrocytes, and some neurons. This activation drives transcriptional programs involving IRF3 and NF-κB, cross-talks with autophagy and cell-fate decisions, and initiates and amplifies neuroinflammation, ultimately accelerating neuronal dysfunction. This review, structured around the framework of DNA sources, signaling mechanisms, cell-fate alterations, and pathological outcomes, systematically summarizes the common mechanisms and disease-specific features of cGAS-STING in pathological conditions such as Alzheimer's disease, Parkinson's disease, ischemic stroke, multiple sclerosis, and other disorders. Furthermore, it summarizes current intervention strategies, including small-molecule inhibitors of cGAS or STING, transcriptional axis blockade, and targeted delivery technologies. It also discusses key issues such as the cell-type-specific roles of cGAS-STING regulation in the CNS, blood-brain barrier penetration, and biomarker development, thereby providing a basis for cGAS-STING-targeted intervention in neuroinflammation.