4.3 Review

Mechanisms and pharmacological applications of ferroptosis: a narrative review

Journal

ANNALS OF TRANSLATIONAL MEDICINE
Volume 9, Issue 19, Pages -

Publisher

AME PUBL CO
DOI: 10.21037/atm-21-1595

Keywords

Ferroptosis; glutathione peroxidase; lipid peroxidation; iron accumulation

Funding

  1. National Natural Science Foundation of China [81871596, 81670260]
  2. Shanghai Pujiang Program [18PJD062]

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Ferroptosis, a recently discovered form of cell death, is closely associated with the pathophysiological processes of various diseases such as tumors and nervous system diseases. Understanding the mechanisms involved in ferroptosis can inform new therapeutic targets and strategies for these diseases.
Objective: We aimed at comprehensively analyzing ferroptosis regulation and its potential role in the treatment of associated diseases. Background: Ferroptosis is a recently discovered form of cell death that involves small molecule-induced oxidative cell death. This process is usually accompanied by large amounts of iron accumulation and lipid peroxidation. Ferroptosis inducers directly or indirectly affect glutathione peroxidase (GPXs) through different pathways. Disturbances in GPXs result in suppressed cellular antioxidant capacities, accumulation of lipid reactive oxygen species (ROS) and oxidative cell death. It has been reported that ferroptosis is closely associated with the pathophysiological processes of many diseases, including tumors, nervous system diseases, ischemia-reperfusion injury, kidney injury and iron metabolism diseases among others. Methods: First, we reviewed the mechanisms of ferroptosis, with emphasis on the characteristics and functions of ferroptosis in multiple pathways. Then, inducers and inhibitors of ferroptosis were reviewed, and their mechanisms of action elucidated. Finally, ferroptosis-associated pathophysiological processes of various diseases were reviewed. Conclusions: Ferroptosis is associated with the occurrence and development of various diseases. Elucidation of the mechanisms involved in ferroptosis will inform new therapeutic targets and strategies for these diseases.

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