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铁死亡:代谢性疾病的新调控机制

Ferroptotic Cell Death: New Regulatory Mechanisms for Metabolic Diseases.

作者信息

Le Yifei, Zhang Zhijie, Wang Cui, Lu Dezhao

机构信息

College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China.

出版信息

Endocr Metab Immune Disord Drug Targets. 2021;21(5):785-800. doi: 10.2174/1871530320666200731175328.

Abstract

BACKGROUND

Cell death is a fundamental biological phenomenon that contributes to the pathogenesis of various diseases. Regulation of iron and iron metabolism has received considerable research interests especially concerning the progression of metabolic diseases.

DISCUSSION

Emerging evidence shows that ferroptosis, a non-apoptotic programmed cell death induced by iron-dependent lipid peroxidation, contributes to the development of complex diseases such as non-alcoholic steatohepatitis, cardiomyopathy, renal ischemia-reperfusion, and neurodegenerative diseases. Therefore, inhibiting ferroptosis can improve the pathophysiology of associated metabolic diseases. This review describes the vital role of ferroptosis in mediating the development of certain metabolic diseases. Besides, the potential risk of iron and ferroptosis in atherosclerosis and cardiovascular diseases is also described. Iron overload and ferroptosis are potential secondary causes of death in metabolic diseases. Moreover, this review also provides potential novel approaches against ferroptosis based on recent research advances.

CONCLUSION

Several controversies exist concerning mechanisms underlying ferroptotic cell death in metabolic diseases, particularly in atherosclerosis. Since ferroptosis participates in the progression of metabolic diseases such as non-alcoholic steatohepatitis (NASH), there is a need to develop new drugs targeting ferroptosis to alleviate such diseases.

摘要

背景

细胞死亡是一种基本的生物学现象,与多种疾病的发病机制相关。铁及铁代谢的调节已引起了相当多的研究兴趣,尤其是在代谢性疾病的进展方面。

讨论

新出现的证据表明,铁死亡是一种由铁依赖性脂质过氧化诱导的非凋亡程序性细胞死亡,与非酒精性脂肪性肝炎、心肌病、肾缺血再灌注和神经退行性疾病等复杂疾病的发展有关。因此,抑制铁死亡可以改善相关代谢性疾病的病理生理学。本综述描述了铁死亡在介导某些代谢性疾病发展中的重要作用。此外,还描述了铁和铁死亡在动脉粥样硬化和心血管疾病中的潜在风险。铁过载和铁死亡是代谢性疾病潜在的次要死亡原因。此外,本综述还根据最近的研究进展提供了对抗铁死亡的潜在新方法。

结论

关于代谢性疾病,特别是动脉粥样硬化中铁死亡性细胞死亡的潜在机制存在一些争议。由于铁死亡参与了非酒精性脂肪性肝炎(NASH)等代谢性疾病的进展,因此需要开发针对铁死亡的新药来缓解此类疾病。

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