Isolevuglandin (IsoLG)

Isolevuglandins (IsoLGs) are a family of highly reactive gamma-ketoaldehydes formed through the rearrangement of endoperoxide intermediates in the isoprostane pathway, primarily during lipid peroxidation of arachidonic acid. Unlike many other lipid-derived mediators, IsoLGs do not act through specific receptors; instead, they rapidly form covalent, irreversible adducts with the primary amines of lysine residues on proteins and with DNA. This chemical modification leads to protein cross-linking, denaturation, and the generation of neoantigens that trigger inflammatory and autoimmune responses. IsoLGs are potent mediators of cellular dysfunction and are implicated in the pathogenesis of various chronic conditions, including hypertension, atherosclerosis, and Alzheimer’s disease. Therapeutic strategies focus on 'scavenging' these molecules using small molecules like 2-hydroxybenzylamine (2-HOBA), which react with IsoLGs much faster than proteins do, thereby preventing the harmful modification of biological macromolecules and attenuating oxidative stress-related damage.

Other names

IsoketalIso-levuglandingamma-ketoaldehydeIsoLGsReactive lipid dicarbonyl

Scavenging of reactive dicarbonyls to prevent covalent modification of proteins and DNA