2 Mechanisms of ferroptosis 2.1 Lipid peroxidation Lipid peroxidation of polyunsaturated fatty acids (PUFAs) in cell membranes is a crucial feature of ferroptosis ( Figure 1 ) ( Figure 1 2.2 Iron dyshomeostasis Iron is a significant material basis for metabolic processes, including mitochondrial respiration, DNA synthesis, and cell signaling, but ferroptosis may occur when it accumulates excessively ( 2+ ) and ferric (Fe 3+ ) ions ( Figure 1 ) ( 2+ , primarily generated from erythrocyte degradation and intestinal absorption, can enhance ROS production through the Fenton reaction, thus facilitating lipid peroxidation ( In vivo , free Fe 2+ enhances the activity of lipoxygenase (LOX) and cytochrome P450 oxidoreductase (POR), enzymes that catalyze polyunsaturated fatty acid-containing phospholipids (PUFA-PLs) oxidation, thereby affecting lipid peroxidation ( 2+ to Fe 3+ , which binds to transferrin (Tf) and endocytosis into cells through the action of transferrin receptor 1 (TfR1) ( 3+ is reduced to Fe 2+ through six-transmembrane epithelial antigen of prostatic 3 (STEAP3) and transferred from endosome/lysosome to the cytosol via apical bivalent metal transporter 1 (DMT1) ( 2+ , thus promoting lipid peroxidation through the Fenton reaction, and the heightened ROS eventually induces ferroptosis ( 2.3 System Xc-/GSH/GPX4 pathway Glutathione (GSH), which mainly includes cysteine, glutamic acid, and glycine, is a vital inhibitor and endogenous antioxidant in ferroptosis ( Figure 1 ) ( 3 Correlation between ferroptosis and pain Previous studies have demonstrated the relationship between ferroptosis and neuropathic pain (NP) and bone pain (BP) ( Figure 2 ) ( Figure 2 Analogously, increased iron levels were detected in the spinal cords of BCP mice ( 4 Ferroptosis and pain-related illness 4.1 Neuropathic pain-related diseases 4.1.1 Multiple sclerosis Multiple sclerosis (MS), a chronic inflammatory and demyelinating disease with the most common and severe symptoms of NP and spasticity, affects approximately 2.1 million people worldwide ( Figure 3 ) (65, 66)
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[DOI] [PMC free article] [PubMed] [Google Scholar] 518.Zuloaga R., Fuentes E.N., Molina A., Valds J.A
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