The STING Signaling: A Novel Target for Central Nervous System Diseases.

The canonical cyclic GMP-AMP (cGAMP) synthase (cGAS)-Stimulator of Interferon Genes (STING) pathway has been widely recognized as a crucial mediator of inflammation in many diseases, including tumors, infections, and tissue damage. STING signaling can also be activated in a cGAS- or cGAMP-independent manner, although the specific mechanisms remain unclear. In-depth studies on the structural and molecular biology of the STING pathway have led to the development of therapeutic strategies involving STING modulators and their targeted delivery. These strategies may effectively penetrate the blood-brain barrier (BBB) and target STING signaling in multiple central nervous system (CNS) diseases in humans. In this review, we outline both canonical and non-canonical pathways of STING activation and describe the general mechanisms and associations between STING activity and CNS diseases. Finally, we discuss the prospects for the targeted delivery and clinical application of STING agonists and inhibitors, highlighting the STING signaling pathway as a novel therapeutic target in CNS diseases.