Ferroptosis: a new target for depression prevention and treatment

Depression, a significant mental health issue, is one of the diseases with the highest disability rates worldwide. The exact etiology of depression remains undetermined, complicating the development of treatment strategies targeting specific mechanisms, and there is currently no effective cure. In this context, ferroptosis may represent a breakthrough in the understanding of depression. Ferroptosis is primarily associated with iron accumulation and lipid peroxidation, and recent studies have revealed its potential association with depression. Clinical evidence suggests that ferroptosis may influence the development and function of the hippocampus through interactions with neuroinflammation. Activated microglia, astrocytes, and neurons are involved in ferroptosis. This review summarizes recent findings on how ferroptosis contributes to depression, including glutathione peroxidase 4 (GPX4), nuclear factor-erythroid 2-related factor 2 (Nrf2), phase separation, and neuroinflammatory pathways, allowing the proposal of some new hypotheses. We hope that exploring the role of ferroptosis in the mechanism of depression will offer a new perspective on the complex biological basis of depression and provide theoretical support for the development of new therapeutic methods.