Therapeutic Effects of Melatonin in the Regulation of Ferroptosis: A Review of Current Evidence.

Ferroptosis is implicated in the pathogenesis of multiple diseases, including neurodegenerative diseases, cardiovascular diseases, kidney pathologies, ischemia-reperfusion injury, and cancer. The current review article highlights the involvement of ferroptosis in traumatic brain injury, acute kidney damage, ethanol-induced liver injury, and PM2.5-induced lung injury. Melatonin, a molecule produced by the pineal gland and many other organs, is well known for its anti- aging, anti-inflammatory, and anticancer properties and is used in the treatment of different diseases. Melatonin's ability to activate anti-ferroptosis pathways including sirtuin (SIRT)6/p- nuclear factor erythroid 2-related factor 2 (Nrf2), Nrf2/ antioxidant responsive element (ARE)/ heme oxygenase (HO-1)/SLC7A11/glutathione peroxidase (GPX4)/ prostaglandin-endoperoxide synthase 2 (PTGS2), extracellular signal-regulated kinase (ERK)/Nrf2, ferroportin (FPN), Hippo/ Yes-associated protein (YAP), Phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) and SIRT6/ nuclear receptor coactivator 4 (NCOA4)/ ferritin heavy chain 1 (FTH1) signaling pathways suggests that it could serve as a valuable therapeutic agent for preventing cell death associated with ferroptosis in various diseases. Further research is needed to fully understand the precise mechanisms by which melatonin regulates ferroptosis and its potential as a therapeutic target.