Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

The Selenoprotein Glutathione Peroxidase 4: From Molecular Mechanisms to Novel Therapeutic Opportunities

Version 1 : Received: 20 February 2022 / Approved: 24 February 2022 / Online: 24 February 2022 (12:05:30 CET)

A peer-reviewed article of this Preprint also exists.

Weaver, K.; Skouta, R. The Selenoprotein Glutathione Peroxidase 4: From Molecular Mechanisms to Novel Therapeutic Opportunities. Biomedicines 2022, 10, 891. Weaver, K.; Skouta, R. The Selenoprotein Glutathione Peroxidase 4: From Molecular Mechanisms to Novel Therapeutic Opportunities. Biomedicines 2022, 10, 891.

Journal reference: Biomedicines 2022, 10, 891
DOI: 10.3390/biomedicines10040891

Abstract

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.

Keywords

Selenoprotein Glutathione Peroxidase 4 (GPX4); Reduced Glutathione (GSH); ferroptosis; lipid peroxidation; ferroptosis modulators; small molecules targeting GPX4

Subject

MEDICINE & PHARMACOLOGY, Oncology & Oncogenics

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