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The chemical basis of ferroptosis.
Nature Chemical Biology ( IF 12.9 ) Pub Date : 2019-11-18 , DOI: 10.1038/s41589-019-0408-1
Marcus Conrad 1 , Derek A Pratt 2
Affiliation  

Lipid peroxidation underlies the mechanism of oxidative cell death now known as ferroptosis. This modality, distinct from other forms of cell death, has been intensely researched in recent years owing to its relevance in both degenerative disease and cancer. The demonstration that it can be modulated by small molecules in multiple pathophysiological contexts offers exciting opportunities for novel pharmacological interventions. Herein, we introduce the salient features of lipid peroxidation, how it can be modulated by small molecules and what principal aspects require urgent investigation by researchers in the field. The central role of non-enzymatic reactions in the execution of ferroptosis will be emphasized, as these processes have hitherto not been generally considered 'druggable'. Moreover, we provide a critical perspective on the biochemical mechanisms that contribute to cell vulnerability to ferroptosis and discuss how they can be exploited in the design of novel therapeutics.

中文翻译:

铁死亡的化学基础。

脂质过氧化是现在称为铁死亡的氧化性细胞死亡机制的基础。这种与其他形式的细胞死亡不同的方式,由于其与退行性疾病和癌症的相关性,近年来得到了深入研究。证明它可以在多种病理生理学背景下被小分子调节,为新的药理学干预提供了令人兴奋的机会。在这里,我们介绍了脂质过氧化的显着特征,它如何被小分子调节以及哪些主要方面需要该领域的研究人员紧急研究。将强调非酶促反应在执行铁死亡中的核心作用,因为这些过程迄今为止通常不被认为是“可药用的”。而且,
更新日期:2019-11-18
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