Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic perspectives

Iron, an essential mineral in the body, is involved in many physiological processes, making maintaining iron homeostasis crucial to overall health. Iron overload and deficiency can cause various disorders and human diseases. 

Ferroptosis, a form of iron-dependent cell death, is characterized by significant peroxidation of lipids. Unlike other types of conventional unprogrammed cell death, ferroptosis is mainly linked to disturbances in iron metabolism, lipid peroxidation and an imbalance in the antioxidant system. Ferroptosis is regulated by transcription, translation and post-translational modifications, which affect cellular sensitivity to ferroptosis. 

Over the past decade, many diseases have been linked to ferroptosis in their etiology, including cancers, metabolic disorders, autoimmune diseases, central nervous system diseases, cardiovascular and musculoskeletal diseases. Ferroptosis-related proteins have become attractive targets for many major human diseases that are currently incurable, and some ferroptosis regulators have shown therapeutic effects in clinical trials, although further validation of their clinical potential is required. 

Therefore, a thorough analysis of ferroptosis and its potential molecular mechanisms in human diseases can provide additional strategies for clinical prevention and treatment. 

In this review, the authors assess recent potential therapeutic targets and promising interventions, providing guidance for future targeted therapies against diseases.