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

期刊

BIOMEDICINES
卷 10, 期 4, 页码 -

出版社

MDPI
DOI: 10.3390/biomedicines10040891

关键词

selenoprotein glutathione peroxidase 4 (GPX4); reduced glutathione (GSH); ferroptosis; lipid peroxidation; ferroptosis modulators; small molecules targeting GPX4

资金

  1. Department of Chemistry and Department Biology at the University of Massachusetts (UMASS)
  2. Lung Cancer Research Foundation
  3. Institute for Applied Life Sciences/Collaborative Cancer Research Grant at UMASS

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This review provides a comprehensive overview of the research on GPX4, highlighting its role as a potential therapeutic target.
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.

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