Ding Lina, Zhang Ruicheng, Du Wenqi, Wang Qingling, Pei Dongsheng
Department of Pathology, Xuzhou Medical University, Xuzhou, China.
Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
J Adv Res. 2024 Dec 20. doi: 10.1016/j.jare.2024.12.028.
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway has been identified as a crucial mechanism in antiviral defense and innate immunity pathway. Ferroptosis, characterized by iron dependence and lipid peroxidation, represents a specialized form of cell death. A burgeoning collection of studies has demonstrated that the cGAS-STING signaling pathway participates in the homeostatic regulation of the organism by modulating ferroptosis-associated enzyme activity or gene expression. Consequently, elucidating the specific roles of the STING signaling pathway and ferroptosis in vivo is vital for targeted disease intervention. This review systematically examines the interactions between the cGAS-STING signaling pathway and ferroptosis, highlighting their influence on disease progression in the contexts of inflammation, injury, and cancerous cell dynamics. Understanding these interactions may provide novel therapeutic strategies. The STING pathway has been implicated in the regulation of various cell death mechanisms, including apoptosis, pyroptosis, necroptosis, autophagy, and ferroptosis. Our focus primarily addresses the role and mechanism of the cGAS-STING signaling pathway and ferroptosis in diseases, limiting discussion of other cell death modalities and precluding a comprehensive overview of the pathway's additional functions.
环磷酸鸟苷-腺苷合成酶（cGAS）-干扰素基因刺激因子（STING）信号通路已被确定为抗病毒防御和先天免疫通路中的关键机制。铁死亡以铁依赖性和脂质过氧化为特征，是一种特殊形式的细胞死亡。越来越多的研究表明，cGAS-STING信号通路通过调节铁死亡相关酶活性或基因表达参与机体的稳态调节。因此，阐明STING信号通路和铁死亡在体内的具体作用对于靶向疾病干预至关重要。本综述系统地研究了cGAS-STING信号通路与铁死亡之间的相互作用，突出了它们在炎症、损伤和癌细胞动态变化背景下对疾病进展的影响。了解这些相互作用可能会提供新的治疗策略。STING通路已被证明参与多种细胞死亡机制的调节，包括凋亡、焦亡、坏死性凋亡、自噬和铁死亡。我们主要关注cGAS-STING信号通路和铁死亡在疾病中的作用和机制，限制对其他细胞死亡方式的讨论，并不对该通路的其他功能进行全面概述。
