The Role of the cGAS-STING Interaction in the Age-Related Inflammation of the Brain
Age-associated leakage of mitochondrial and nuclear DNA activates the cGAS sensor and downstream STING signaling, producing chronic type I interferon and pro-inflammatory responses in the brain that drive neurodegenerative pathology (Alzheimer's, Parkinson's, ALS). Preclinical cGAS or STING inhibitors reverse cognitive decline and neuropathology in models, but translating these findings requires careful degree- and cell-type-specific modulation because the pathway is essential for host defense and is sensitive to DNA source, oxidation state, and mode of release.
Why it mattersPreclinical cGAS-STING inhibitors reversed cognitive decline in models, prompting careful dose- and cell-specific modulation to avoid.