Weaver Kamari, Skouta Rachid
Department of Biology, University of Massachusetts, Amherst, MA 01003, USA.
Biomedicines. 2022 Apr 13;10(4):891. doi: 10.3390/biomedicines10040891.
The selenoprotein glutathione peroxidase 4 (GPX4) is one of the main antioxidant mediators in the human body. Its central function involves the reduction of complex hydroperoxides into their respective alcohols often using reduced Glutathione (GSH) as a reducing agent. GPX4 has become a hotspot therapeutic target in biomedical research following its characterization as a chief regulator of ferroptosis, and its subsequent recognition as a specific pharmacological target for the treatment of an extensive variety of human diseases including cancers and neurodegenerative disorders. Several recent studies have provided insights into how GPX4 is distinguished from the rest of the glutathione peroxidase family, the unique biochemical properties of GPX4, how GPX4 is related to lipid peroxidation and ferroptosis, and how the enzyme may be modulated as a potential therapeutic target. This current report aims to review the literature underlying all these insights and present an up-to-date perspective on the current understanding of GPX4 as a potential therapeutic target.
硒蛋白谷胱甘肽过氧化物酶4（GPX4）是人体主要的抗氧化介质之一。其核心功能包括通常利用还原型谷胱甘肽（GSH）作为还原剂，将复杂的氢过氧化物还原为各自的醇类。自从GPX4被确定为铁死亡的主要调节因子，并随后被认定为治疗包括癌症和神经退行性疾病在内的多种人类疾病的特定药理学靶点以来，它已成为生物医学研究中的一个热点治疗靶点。最近的几项研究深入探讨了GPX4如何与谷胱甘肽过氧化物酶家族的其他成员区分开来、GPX4独特的生化特性、GPX4如何与脂质过氧化和铁死亡相关，以及该酶作为潜在治疗靶点可能如何被调节。本报告旨在回顾所有这些见解背后的文献，并就目前对GPX4作为潜在治疗靶点的理解提供最新观点。
