Rheumatoid arthritis (RA) is a common systemic autoimmune disease with a prevalence of about 1% in which genetic and environmental risk factors both participate in performance of disease. Though several studies contributed in identifying its etiology and pathogenesis, the underlying mechanisms are still unknown. To date, so as palliative for RA, cure strategies are still popular. Hypoxia and oxidative stress are implicated to RA development and subsequent ROS-mediated cell death which is a critical feature for RA progression. As for cell death and lipid peroxidation, ferroptosis is a newly discovered, iron-dependent, and non-apoptotic cell death which draws various attention due to its potential strategies for cancer therapy. Meanwhile, ferroptosis-suppressor-protein 1 (FSP1) is recently identified as a seminal breakthrough owing to its property of versus ferroptosis. By virtue of the complicated research progress on FSP1 with ferroptosis, in this review, we summarize the whole region of relevance between ROS and RA. Taken together, we hypothesize that ROS accompanied with ferroptosis may function as a reciprocal with cell death that interplays with RA; besides, FSP1 might become a potential therapeutic target for RA because of its potential interaction with TNF-α/ROS-positive feedback loop. This review systematically concludes the previous understandings about identification of ROS and FSP1 and, in turn, aims to provide references for further achievements of them and hints on elucidation of its thorough underlying mechanisms.

中文翻译：

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类风湿性关节炎中 ROS 依赖性脂质过氧化和依赖抗氧化剂铁死亡抑制蛋白 1：潜在治疗的隐秘线索。


类风湿性关节炎(RA)是一种常见的全身性自身免疫性疾病，患病率约为1%，遗传和环境危险因素均参与疾病的表现。尽管多项研究有助于确定其病因和发病机制，但其潜在机制仍不清楚。迄今为止，作为 RA 的姑息疗法，治疗策略仍然很受欢迎。缺氧和氧化应激与 RA 的发展和随后的 ROS 介导的细胞死亡有关，这是 RA 进展的关键特征。至于细胞死亡和脂质过氧化，铁死亡是一种新发现的、铁依赖性、非凋亡性细胞死亡，由于其潜在的癌症治疗策略而引起了广泛的关注。与此同时，铁死亡抑制蛋白 1 (FSP1) 最近因其抗铁死亡的特性而被认为是一项重大突破。凭借FSP1与铁死亡的复杂研究进展，在这篇综述中，我们总结了ROS和RA之间的整个相关领域。综上所述，我们假设 ROS 伴随铁死亡可能与细胞死亡相互作用，并与 RA 相互作用；此外，FSP1 由于其与 TNF-α/ROS 正反馈环的潜在相互作用，可能成为 RA 的潜在治疗靶点。本综述系统总结了前人对ROS和FSP1识别的认识，旨在为进一步研究ROS和FSP1的研究成果提供参考，并为阐明其深层机制提供线索。