FGF–FGFR Signaling in Parkinson’s Disease: Mechanistic Links to Ferroptosis and Neuroprotection

Parkinson's disease (PD) is characterized by progressive degeneration of the nigrostriatal dopaminergic system and α-synuclein (α-syn) pathology, with disease progression driven by convergent mechanisms including neuroinflammation, mitochondrial injury, oxidative stress, and regulated cell-death programs such as ferroptosis. Fibroblast growth factors (FGFs) and fibroblast growth factor receptors (FGFRs) constitute a key signaling system in the central nervous system, influencing not only neuronal survival and glial states but also intersecting with networks governing redox homeostasis and iron metabolism. Accumulating evidence indicates that, beyond classical neurotrophic actions, FGF-FGFR signaling can modulate mitochondrial quality control, glial inflammatory activation, and lipid peroxidation-related processes, thereby reshaping cellular susceptibility to ferroptotic injury. This review summarizes current advances in understanding FGF signaling networks in Parkinson's disease, synthesizes their potential mechanistic links to the interplay among neuroinflammation, mitochondrial dysfunction, and redox imbalance as well as to ferroptosis regulation, and discusses the experimental basis and translational challenges of targeting the FGF pathway as a disease-modifying therapeutic strategy.