Targeting GPX4-dependent ferroptosis by natural compounds in multiple sclerosis

Multiple sclerosis (MS) is an autoimmune-mediated, heterogeneous, multifactorial central nervous system degenerative disease influenced by genetics and environment. Ferroptosis, an iron-dependent lipid peroxidation/reactive oxygen species-induced programmed cell death, exacerbates MS pathology. Glutathione peroxidase 4 (GPX4) regulates ferroptosis by clearing peroxides to sustain cells. Targeting GPX4-mediated ferroptosis, especially via safe, potent natural compounds, is a promising MS treatment. This review explores GPX4-dependent ferroptosis's role in MS progression and summarizes natural compounds for MS therapy.