cGAS–STING Signaling in Central Nervous System Diseases: Neuroinflammatory Mechanisms and Immune Regulation

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway has emerged as a critical cytosolic DNA-sensing mechanism that orchestrates innate immune activation in response to cellular stress. In the central nervous system (CNS), this pathway demonstrates highly context-specific and cell-type-dependent functions, ranging from promoting neuroinflammation in neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), to modulating immune surveillance and therapeutic responsiveness in glioma. This review systematically delineates the molecular mechanisms, activation patterns, and regulatory networks of cGAS-STING signaling in the CNS. We highlight its dualistic roles in both inflammatory exacerbation and antitumor immunity, and further discuss recent advances in therapeutic strategies, including pharmacological modulators, blood-brain barrier (BBB)-penetrating delivery platforms, and nanotechnology-based precision interventions. Finally, we propose future directions focused on decoding tissue-specific immunodynamics and developing spatiotemporally controlled, multiorgan immunoregulatory frameworks. Together, this review underscores cGAS-STING as a promising therapeutic axis in the evolving landscape of neuroimmunology.