人类疾病中的铁稳态和铁变态反应:机制和治疗前景

IF 40.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Signal Transduction and Targeted Therapy Pub Date : 2024-10-14 DOI:10.1038/s41392-024-01969-z
Qin Ru, Yusheng Li, Lin Chen, Yuxiang Wu, Junxia Min, Fudi Wang
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摘要

铁是人体内不可或缺的矿物质,参与多种生理过程,因此维持铁的平衡对整体健康至关重要。铁过量和缺铁都会导致各种失调和人类疾病。铁中毒(Ferroptosis)是一种依赖于铁的细胞死亡形式,其特点是脂质的广泛过氧化。与其他类型的经典非程序性细胞死亡不同,铁变态反应主要与铁代谢紊乱、脂质过氧化和抗氧化系统失衡有关。铁变态反应通过转录、翻译和翻译后修饰进行调控,这些都会影响细胞对铁变态反应的敏感性。过去十多年来,许多疾病的病因都与铁蛋白沉积有关,包括癌症、代谢紊乱、自身免疫性疾病、中枢神经系统疾病、心血管疾病和肌肉骨骼疾病。与铁突变相关的蛋白质已成为许多目前无法治愈的重大人类疾病的诱人靶标,一些铁突变调节剂已在临床试验中显示出治疗效果,但其临床潜力还需要进一步验证。因此,深入分析铁蛋白沉积及其在人类疾病中的潜在分子机制可能会为临床预防和治疗提供更多策略。在这篇综述中,我们讨论了体内铁平衡的生理意义、嗜铁细胞增多症对人类疾病的病因和发展的潜在作用,以及支持将嗜铁细胞增多症作为靶向治疗方法的证据。重要的是,我们评估了最近的潜在治疗靶点和有希望的干预措施,为未来针对人类疾病的靶向治疗提供指导。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects

Iron, an essential mineral in the body, is involved in numerous physiological processes, making the maintenance of iron homeostasis crucial for overall health. Both iron overload and deficiency can cause various disorders and human diseases. Ferroptosis, a form of cell death dependent on iron, is characterized by the extensive peroxidation of lipids. Unlike other kinds of classical unprogrammed cell death, ferroptosis is primarily linked to disruptions in iron metabolism, lipid peroxidation, and antioxidant system imbalance. Ferroptosis is regulated through transcription, translation, and post-translational modifications, which affect cellular sensitivity to ferroptosis. Over the past decade or so, numerous diseases have been linked to ferroptosis as part of their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous system diseases, cardiovascular diseases, and musculoskeletal diseases. Ferroptosis-related proteins have become attractive targets for many major human diseases that are currently incurable, and some ferroptosis regulators have shown therapeutic effects in clinical trials although further validation of their clinical potential is needed. Therefore, in-depth analysis of ferroptosis and its potential molecular mechanisms in human diseases may offer additional strategies for clinical prevention and treatment. In this review, we discuss the physiological significance of iron homeostasis in the body, the potential contribution of ferroptosis to the etiology and development of human diseases, along with the evidence supporting targeting ferroptosis as a therapeutic approach. Importantly, we evaluate recent potential therapeutic targets and promising interventions, providing guidance for future targeted treatment therapies against human diseases.

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来源期刊
Signal Transduction and Targeted Therapy
Signal Transduction and Targeted Therapy Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
44.50
自引率
1.50%
发文量
384
审稿时长
5 weeks
期刊介绍: Signal Transduction and Targeted Therapy is an open access journal that focuses on timely publication of cutting-edge discoveries and advancements in basic science and clinical research related to signal transduction and targeted therapy. Scope: The journal covers research on major human diseases, including, but not limited to: Cancer,Cardiovascular diseases,Autoimmune diseases,Nervous system diseases.
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