Ferroptosis in microglial activation: a systematic review and multidata comparison

Ferroptosis is a redox-driven and iron-dependent type of programmed cell death, with lipid peroxidation as a central and required feature of the process. During ferroptosis, cells exert strong proinflammatory effects, suggesting that ferroptosis may play a role in the regulation of inflammation and immune response. However, very few studies have investigated the process of ferroptosis and lipid peroxidation in microglia, the innate immune cells of the brain. In this review, we summarize the concept of ferroptosis and present a list of 120 ferroptosis-relevant proteins, which includes over twice as many entries as the current Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway for ferroptosis. We compare our manually compiled list with microglial activation signatures reported by us and others, revealing ferroptosis-relevant changes in models for microglial activation. Finally, we highlight a selection of ferroptosis-relevant proteins as potential biomarker candidates for ferroptosis.