Decoding the key mechanisms of ferroptosis and inflammation: Emerging therapeutic targets for Alzheimer's disease

Abstract

Alzheimer's disease (AD) is a common progressive neurodegenerative disorder characterized by excessive amyloid-β (Aβ) deposition leading to the formation of senile plaques and hyperphosphorylation of tau protein resulting in NFTs. Ferroptosis, a newly identified form of programmed cell death, promotes neuroinflammation through mechanisms such as iron metabolism dysregulation, lipid peroxidation, and redox imbalance. Neuroinflammation, in turn, accelerates ferroptotic processes, creating a vicious cycle that drives the progression of neurodegenerative diseases. Recent studies have revealed a close association between ferroptosis and neuroinflammation in AD, and several ferroptosis-targeted agents have shown promising therapeutic effects in AD cell and animal models. This review explores the pathogenesis of ferroptosis in AD and elucidates the mechanistic role of the regulatory interplay between ferroptosis and neuroinflammation in AD, recent advances in ferroptosis-targeted therapeutic strategies are also discussed. Together, these insights may offer new perspectives for treating this devastating disorder.