Targeting Ferroptosis in Parkinson’s Disease: Mechanisms and Emerging Therapeutic Strategies

Abstract

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra and the accumulation of α-synuclein in the brain. Ferroptosis, a recently identified form of regulated cell death, is critical in PD pathogenesis due to its association with iron deposition, overproduction of reactive oxygen species, iron-dependent lipid peroxidation and impaired lipid peroxidation clearance. This cell death mechanism is closely linked to several pathogenic processes in PD, including α-synuclein aggregation, oxidative stress, mitochondrial dysfunction, microglia-induced neuroinflammation, and neuromelanin accumulation. Given the significant role of ferroptosis in these mechanisms, there is increasing interest in targeting ferroptosis for PD treatment. Several drugs have shown potential in alleviating PD symptoms by inhibiting ferroptosis. This review aims to consolidate current knowledge on ferroptosis in PD and assess the therapeutic potential of anti-ferroptosis drugs, highlighting promising directions for future research and clinical applications.