FGF22/FGFR2/YAP modulates ferroptosis to suppress neurodegeneration and cognitive impairment in Alzheimer's disease.

Ferroptosis, a programmed cell death triggered by iron accumulation and lipid peroxidation, has been increasingly recognized as a critical mechanism underlying neurodegenerative processes, including Alzheimer's disease (AD). The mechanosensitive regulator YAP is implicated in AD progression and ferroptosis. Here we confirmed that FGF22, a fibroblast growth factor, amelitorated cognitive deficits in β-Amyloid (1-42) (Aβ1-42) treated AD model mice through the FGFR2/YAP pathway, which was further ascertained by various biochemical analyses. Additionally, FGF22 treatment effectively reduced ferroptosis and neuronal apoptosis, thereby attenuating synaptic impairments and neuronal injury in the AD model mice and Aβ1-42-exposed HT22 cells. Collectively, the data presented herein implicate FGF22 as a potential neuroprotective agent in AD models, with its efficacy likely mediated through engaging of the FGFR2/YAP signaling axis.