Ferroptosis in neurological diseases: moving towards therapeutic intervention

Ferroptosis is a regulated cell death driven by iron-dependent lipid peroxidation and has been implicated in major neurological diseases. The brain is enriched in polyunsaturated fatty acids (PUFAs) and iron, which makes it particularly susceptible to lipid peroxidation, leading to ferroptosis. In neurological diseases such as Alzheimer's disease (AD) and stroke, such mechanisms are dysregulated and contribute to neuronal loss. Physiologically, the lipid peroxidation resistance systems in the brain, including defenses (such as SOD, CAT, Prxs, GPxs) and repair systems (such as GPx4, FSP1), prevent ferroptosis and repair damaged phospholipid membranes. However, the efficacy of endogenous resistance systems is often compromised in pathological states, positioning exogenous antioxidants as promising therapeutic candidates. Future research could optimize the delivery of these compounds and explore new candidates that specifically target the ferroptosis signaling pathway to prevent neurodegeneration occurring in neurological diseases.