The role of cGAS-STING signaling in ischemic stroke: From immune response to therapeutic targeting

Abstract

Stroke, a debilitating condition with limited treatment options, presents a significant therapeutic challenge. A comprehensive grasp of stroke pathophysiology is imperative for designing newer and more effective therapeutic approaches. Notably, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has emerged as a central orchestrator of the poststroke immune response. It regulates pivotal processes, including immune cell activation, cytokine production, neuroinflammation, apoptosis, and tissue regeneration. Modulating this pathway shows immense potential in improving stroke outcomes, necessitating the development of selective inhibitors and activators. This review provides an overview of the cGAS-STING pathway's role in ischemic stroke and explores emerging therapies, including cGAS and STING inhibitors and STING agonist preconditioning. It also addresses challenges like specificity, timing, and off-target effects.

Keywords: STING; cGAS; cell death; interferon-β; ischemic stroke; neuroinflammation.