Cellular lipid membranes and lipid radicals

Cellular lipid membranes are essential structural barriers composed of phospholipids, which are frequently enriched with polyunsaturated fatty acids (PUFAs) that are highly vulnerable to oxidation (PubMed: 22624696). When reactive oxygen species interact with these PUFAs, they generate lipid radicals, initiating a chain reaction of lipid peroxidation that compromises membrane integrity and function (PubMed: 31105042). This oxidative damage is a hallmark of ferroptosis, an iron-dependent form of regulated cell death implicated in various pathologies including neurodegeneration and ischemia (PubMed: 28753428). Therapeutic strategies targeting this process focus on radical-trapping antioxidants (RTAs) and small molecules like ferrostatin-1 that neutralize lipid peroxyl radicals, thereby halting the peroxidative chain (PubMed: 27345442). These targets are of significant interest in treating neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, as well as mitigating tissue damage during stroke and myocardial infarction (PubMed: 30306838).

Other names

Membrane phospholipidsLipid peroxyl radicalsPolyunsaturated fatty acidsPUFA-phospholipidsCell membrane lipids

Radical trapping antioxidants (RTAs) inhibit the propagation of lipid peroxidation by donating a hydrogen atom to lipid peroxyl radicals (LOO•), thereby neutralizing them into relatively stable hydroperoxides and preventing the destruction of the phospholipid bilayer (PubMed: 31105042).