AI Article Synopsis

  • Ferroptosis is a type of cell death triggered by iron-related damage to lipids, leading to membrane breakdown and is linked to various diseases like cancer and neurodegenerative disorders.
  • Despite progress in understanding ferroptosis mechanisms, including genetic and epigenetic factors, the precise regulatory pathways and how to develop effective therapies targeting this process are still unclear.
  • The review highlights the need for further research to clarify the role of ferroptosis in diseases and suggests potential strategies for clinical monitoring and treatment development.

Article Abstract

Ferroptosis is a nonapoptotic form of cell death characterized by iron-dependent lipid peroxidation in membrane phospholipids. Since its identification in 2012, extensive research has unveiled its involvement in the pathophysiology of numerous diseases, including cancers, neurodegenerative disorders, organ injuries, infectious diseases, autoimmune conditions, metabolic disorders, and skin diseases. Oxidizable lipids, overload iron, and compromised antioxidant systems are known as critical prerequisites for driving overwhelming lipid peroxidation, ultimately leading to plasma membrane rupture and ferroptotic cell death. However, the precise regulatory networks governing ferroptosis and ferroptosis-targeted therapy in these diseases remain largely undefined, hindering the development of pharmacological agonists and antagonists. In this review, we first elucidate core mechanisms of ferroptosis and summarize its epigenetic modifications (e.g., histone modifications, DNA methylation, noncoding RNAs, and N6-methyladenosine modification) and nonepigenetic modifications (e.g., genetic mutations, transcriptional regulation, and posttranslational modifications). We then discuss the association between ferroptosis and disease pathogenesis and explore therapeutic approaches for targeting ferroptosis. We also introduce potential clinical monitoring strategies for ferroptosis. Finally, we put forward several unresolved issues in which progress is needed to better understand ferroptosis. We hope this review will offer promise for the clinical application of ferroptosis-targeted therapies in the context of human health and disease.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577302PMC
http://dx.doi.org/10.1002/mco2.70010DOI Listing

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