Department of Neurology and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Center for Biotherapy, 610041, Chengdu, China.
West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, 610041, Chengdu, China.
Signal Transduct Target Ther. 2021 Feb 3;6(1):49. doi: 10.1038/s41392-020-00428-9.
Ferroptosis is an iron-dependent cell death, which is different from apoptosis, necrosis, autophagy, and other forms of cell death. The process of ferroptotic cell death is defined by the accumulation of lethal lipid species derived from the peroxidation of lipids, which can be prevented by iron chelators (e.g., deferiprone, deferoxamine) and small lipophilic antioxidants (e.g., ferrostatin, liproxstatin). This review summarizes current knowledge about the regulatory mechanism of ferroptosis and its association with several pathways, including iron, lipid, and cysteine metabolism. We have further discussed the contribution of ferroptosis to the pathogenesis of several diseases such as cancer, ischemia/reperfusion, and various neurodegenerative diseases (e.g., Alzheimer's disease and Parkinson's disease), and evaluated the therapeutic applications of ferroptosis inhibitors in clinics.
铁死亡是一种铁依赖性的细胞死亡方式，与细胞凋亡、坏死、自噬等其他形式的细胞死亡不同。铁死亡细胞死亡的过程是由脂质过氧化衍生的致命脂质物种的积累所定义的，铁螯合剂（如地拉罗司、去铁胺）和小疏水性抗氧化剂（如 ferrostatin、liproxstatin）可以预防这种积累。本文综述了铁死亡的调控机制及其与铁、脂质和半胱氨酸代谢等多种途径的关联的最新知识。我们还进一步讨论了铁死亡对包括癌症、缺血/再灌注和各种神经退行性疾病（如阿尔茨海默病和帕金森病）在内的几种疾病发病机制的贡献，并评估了铁死亡抑制剂在临床上的治疗应用。
