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铁死亡的药理学抑制作为神经退行性疾病和中风的治疗靶点。

Pharmacological Inhibition of Ferroptosis as a Therapeutic Target for Neurodegenerative Diseases and Strokes.

机构信息

Department of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, Beijing, 100049, P. R. China.

Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, 430000, P. R. China.

出版信息

Adv Sci (Weinh). 2023 Aug;10(24):e2300325. doi: 10.1002/advs.202300325. Epub 2023 Jun 21.

Abstract

Emerging evidence suggests that ferroptosis, a unique regulated cell death modality that is morphologically and mechanistically different from other forms of cell death, plays a vital role in the pathophysiological process of neurodegenerative diseases, and strokes. Accumulating evidence supports ferroptosis as a critical factor of neurodegenerative diseases and strokes, and pharmacological inhibition of ferroptosis as a therapeutic target for these diseases. In this review article, the core mechanisms of ferroptosis are overviewed and the roles of ferroptosis in neurodegenerative diseases and strokes are described. Finally, the emerging findings in treating neurodegenerative diseases and strokes through pharmacological inhibition of ferroptosis are described. This review demonstrates that pharmacological inhibition of ferroptosis by bioactive small-molecule compounds (ferroptosis inhibitors) could be effective for treatments of these diseases, and highlights a potential promising therapeutic avenue that could be used to prevent neurodegenerative diseases and strokes. This review article will shed light on developing novel therapeutic regimens by pharmacological inhibition of ferroptosis to slow down the progression of these diseases in the future.

摘要

新出现的证据表明,铁死亡是一种独特的受调控的细胞死亡方式,其形态学和机制与其他形式的细胞死亡明显不同,在神经退行性疾病和中风的病理生理过程中起着至关重要的作用。越来越多的证据支持铁死亡是神经退行性疾病和中风的关键因素,铁死亡的药理学抑制是这些疾病的治疗靶点。在这篇综述文章中,概述了铁死亡的核心机制,并描述了铁死亡在神经退行性疾病和中风中的作用。最后,描述了通过药理学抑制铁死亡来治疗神经退行性疾病和中风的新发现。本综述表明,通过生物活性小分子化合物(铁死亡抑制剂)抑制铁死亡对这些疾病的治疗可能是有效的,并强调了一种潜在的有前途的治疗途径,可用于预防神经退行性疾病和中风。本文综述将为未来通过药理学抑制铁死亡开发新的治疗方案以减缓这些疾病的进展提供思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6443/10460905/efad3c5aa09b/ADVS-10-2300325-g012.jpg

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