The First Affiliated Hospital, Institute of Translational Medicine, The Second Affiliated Hospital, School of Public Health, Cancer Center, State Key Laboratory of Experimental Hematology, Zhejiang University School of Medicine, Hangzhou, China.
Signal Transduct Target Ther. 2023 Sep 21;8(1):372. doi: 10.1038/s41392-023-01606-1.
Ferroptosis is an iron-dependent form of regulated cell death with distinct characteristics, including altered iron homeostasis, reduced defense against oxidative stress, and abnormal lipid peroxidation. Recent studies have provided compelling evidence supporting the notion that ferroptosis plays a key pathogenic role in many diseases such as various cancer types, neurodegenerative disease, diseases involving tissue and/or organ injury, and inflammatory and infectious diseases. Although the precise regulatory networks that underlie ferroptosis are largely unknown, particularly with respect to the initiation and progression of various diseases, ferroptosis is recognized as a bona fide target for the further development of treatment and prevention strategies. Over the past decade, considerable progress has been made in developing pharmacological agonists and antagonists for the treatment of these ferroptosis-related conditions. Here, we provide a detailed overview of our current knowledge regarding ferroptosis, its pathological roles, and its regulation during disease progression. Focusing on the use of chemical tools that target ferroptosis in preclinical studies, we also summarize recent advances in targeting ferroptosis across the growing spectrum of ferroptosis-associated pathogenic conditions. Finally, we discuss new challenges and opportunities for targeting ferroptosis as a potential strategy for treating ferroptosis-related diseases.
铁死亡是一种铁依赖性的细胞死亡形式，具有独特的特征，包括铁稳态改变、抗氧化应激能力降低以及异常的脂质过氧化。最近的研究提供了令人信服的证据，支持铁死亡在许多疾病中发挥关键致病作用的观点，如各种癌症类型、神经退行性疾病、涉及组织和/或器官损伤的疾病、炎症性和传染性疾病。尽管铁死亡的确切调控网络在很大程度上尚不清楚，特别是在各种疾病的起始和进展方面，但铁死亡被认为是进一步开发治疗和预防策略的可靠靶点。在过去的十年中，在开发用于治疗这些与铁死亡相关疾病的药理学激动剂和拮抗剂方面取得了相当大的进展。在这里，我们详细概述了我们目前对铁死亡、其病理作用以及在疾病进展过程中的调控的认识。我们重点介绍了在临床前研究中使用靶向铁死亡的化学工具，并总结了近年来针对不断增加的与铁死亡相关的致病条件靶向铁死亡的最新进展。最后，我们讨论了将铁死亡作为治疗铁死亡相关疾病的潜在策略的新挑战和机遇。
