Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Raebareli (NIPER-R), Transit Campus, Bijnor-Sisendi Road, Sarojini Nagar, Near CRPF Base Camp, Lucknow, UP 226002, India.
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Raebareli (NIPER-R), Transit Campus, Bijnor-Sisendi Road, Sarojini Nagar, Near CRPF Base Camp, Lucknow, UP 226002, India.
Drug Discov Today. 2023 Nov;28(11):103792. doi: 10.1016/j.drudis.2023.103792. Epub 2023 Sep 30.
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.
中风是一种具有有限治疗选择的致残性疾病，带来了重大的治疗挑战。为了设计更新、更有效的治疗方法，全面了解中风的病理生理学至关重要。值得注意的是，环鸟苷酸-腺苷酸合成酶（cGAS）-干扰素基因刺激物（STING）信号通路已成为中风后免疫反应的核心协调者。它调节包括免疫细胞激活、细胞因子产生、神经炎症、细胞凋亡和组织再生在内的关键过程。调节该通路在改善中风预后方面具有巨大潜力，因此需要开发选择性抑制剂和激活剂。本综述概述了 cGAS-STING 通路在缺血性中风中的作用，并探讨了新兴疗法，包括 cGAS 和 STING 抑制剂以及 STING 激动剂预处理。它还解决了特异性、时机和脱靶效应等挑战。
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