Dataset Information

Mechanisms and pharmacological applications of ferroptosis: a narrative review.

ABSTRACT:

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.

SUBMITTER: Zhang JJ

PROVIDER: S-EPMC8573439 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

Mechanisms and pharmacological applications of ferroptosis: a narrative review.

Zhang Jing-Jing JJ Du Jing J Kong Ni N Zhang Guang-Yu GY Liu Meng-Zhen MZ Liu Chong C

Annals of translational medicine 20211001 19

<h4>Objective</h4>We aimed at comprehensively analyzing ferroptosis regulation and its potential role in the treatment of associated diseases.<h4>Background</h4>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 G ...[more]

PMID: 34805365

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Project description:Background and objectiveFerroptosis is a recently discovered form of cell death which differs from other forms of cell death in terms of morphology, biochemistry, and regulatory mechanisms. Ferroptosis is regulated by a complex system and the precise molecular mechanisms are still being elucidated. Over the past few years, extensive research has revealed that the essence of ferroptosis is iron-dependent accumulation of lipid hydroperoxides induced by oxidative stress, and the System Xc-glutathione (GSH)-glutathione peroxidase 4 (GPX4) pathway is the main ferroptosis prevention system. Meanwhile, other antioxidant systems have also been implicated in regulating ferroptosis, including the transsulfuration pathway, mevalonate pathway, ferroptosis inhibitory protein 1 (FSP1)-Coenzyme Q10 (CoQ10) pathway, dihydroorotate dehydrogenase (DHODH)-dihydroubiquione (CoQH2) pathway, and GTP cyclohydrolase-1 (GCH1)-tetrahydrobiopterin (BH4) pathway. This article reviews the molecular mechanisms of ferroptosis and its critical role in antioxidant systems, aiming to reveal that antioxidation is an important method of inhibiting ferroptosis and to provide a new direction for the treatment of ferroptosis-related diseases.MethodsWe searched all original papers and reviews about the molecular mechanisms of ferroptosis in antioxidant systems using PubMed to November 2021. The search terms used included: 'ferroptosis', 'ferroptosis inducers', 'ferroptosis inhibitors', 'ferroptosis and GSH', 'ferroptosis and GPX4', 'ferroptosis and System Xc-', 'SLC7A11', 'P53', 'NRF2 and ferroptosis', 'iron metabolism', 'lipid peroxidation', 'antioxidant systems', 'transsulfuration pathway', 'mevalonate pathway', 'FSP1-CoQ10', 'DHODH-CoQH2', and 'GCH1-BH4'.Key content and findingsWe first introduced the origin of ferroptosis and its common inhibitors and inducers. Next, we discussed the molecular mechanisms of ferroptosis and its role in antioxidant systems in existing studies. Finally, we briefly summarized the relationship between ferroptosis and diseases. It reveals that antioxidation is an important method of inhibiting ferroptosis.ConclusionsThis review discusses the recent rapid progress in the understanding of the molecular mechanisms of ferroptosis and its role in several antioxidant systems.

Dataset Information

Mechanisms and pharmacological applications of ferroptosis: a narrative review.

Objective

Background

Methods

Conclusions

Publications

Mechanisms and pharmacological applications of ferroptosis: a narrative review.

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