Scientists reveal how cGAS-STING fuels brain inflammation and neurodegeneration

A major immune pathway once known for detecting DNA damage is now being linked to brain aging, glial dysfunction, and neurodegenerative disease, raising hopes for more targeted therapies.

A recent review article published in the Journal of Clinical Investigation discusses the expanding roles of the cyclic GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway in neuroinflammation.

Nucleic acid sensing is central to innate immunity. Pattern recognition receptors (PRRs) are molecular sentinels that detect endogenous signals and pathogen-derived nucleic acids. Various PRRs function as DNA sensors, including cGAS, which can directly detect double-stranded DNA (dsDNA) in the nucleus and cytosol independent of sequence. cGAS activates STING after binding to dsDNA, inducing a strong type I interferon (IFN-I) response.

Neuroinflammation is a hallmark of neurological diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD), and Huntington’s disease. The cGAS-STING pathway has emerged as a regulator of anti-tumor immunity, tumorigenesis, and neuroinflammation, and its dysregulation is implicated in brain aging and neurodegenerative diseases. In this review, researchers summarized the role and functions of cGAS-STING signaling in the brain and its therapeutic potential.