Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Raebareli (NIPER-R), Lucknow, India.
Expert Opin Drug Discov. 2023 Jul-Dec;18(10):1133-1149. doi: 10.1080/17460441.2023.2244409. Epub 2023 Aug 10.
Ischemic stroke is a significant global health challenge with limited treatment options. Neuroinflammation, driven by microglial activation, plays a critical role in stroke pathophysiology. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has emerged as a key player in microglial activation, sterile neuroinflammation, and cell death following stroke. Understanding the interplay between this pathway and stroke pathophysiology is crucial for exploring newer therapeutics for stroke patients.
This review discusses the pivotal role of the cGAS-STING pathway in ischemic stroke. It explores the interplay between cGAS-STING activation, neuroinflammation, microglia activation, M2 polarization, neutrophil infiltration, and cytokine release. Additionally, the authors examine its contributions to various cell death programs (pyroptosis, apoptosis, necroptosis, lysosomal cell death, autophagy, and ferroptosis). The review summarizes recent studies on targeting cGAS-STING signaling in stroke, highlighting the therapeutic potential of small molecule inhibitors and RNA-based approaches in mitigating neuroinflammation, preventing cell death, and improving patient outcomes.
Understanding cGAS-STING signaling in ischemic stroke offers an exciting avenue for drug discovery. Targeting this pathway holds promise for developing novel therapeutics that effectively mitigate neuroinflammation, prevent cell death, and enhance patient outcomes. Further research and development of therapeutic strategies are warranted to fully exploit the potential of this pathway as a therapeutic target for stroke.
缺血性中风是一个具有全球性的重大健康挑战，其治疗选择有限。小胶质细胞的激活所驱动的神经炎症在中风病理生理学中起着关键作用。环鸟苷酸-腺苷酸合酶（cGAS）-干扰素基因刺激物（STING）信号通路已成为小胶质细胞激活、无菌性神经炎症以及中风后细胞死亡的关键因素。了解该通路与中风病理生理学之间的相互作用对于探索中风患者的新型治疗方法至关重要。
本综述讨论了 cGAS-STING 通路在缺血性中风中的关键作用。它探讨了 cGAS-STING 激活、神经炎症、小胶质细胞激活、M2 极化、中性粒细胞浸润和细胞因子释放之间的相互作用。此外，作者还研究了其对各种细胞死亡程序（细胞焦亡、细胞凋亡、坏死性凋亡、溶酶体细胞死亡、自噬和铁死亡）的贡献。该综述总结了最近关于在中风中靶向 cGAS-STING 信号的研究，强调了小分子抑制剂和 RNA 为基础的方法在减轻神经炎症、预防细胞死亡和改善患者预后方面的治疗潜力。
了解 cGAS-STING 信号在缺血性中风中的作用为药物发现提供了一个令人兴奋的途径。靶向该通路为开发有效的治疗方法提供了希望，这些方法可以减轻神经炎症、预防细胞死亡并改善患者预后。需要进一步的研究和治疗策略的开发，以充分利用该通路作为中风治疗靶点的潜力。
