Malondialdehyde-modified protein (MDA-modified protein) (MDA-modified protein)

Malondialdehyde (MDA)-modified proteins are a prominent class of oxidation-specific epitopes (OSEs) that form when malondialdehyde, a reactive byproduct of lipid peroxidation, covalently binds to protein residues such as lysine (Witztum & Lichtman, 2014). These modifications transform self-proteins into neoantigens, which are recognized by the innate immune system as damage-associated molecular patterns (DAMPs) (Binder et al., 2002). On cell surfaces, including those of apoptotic cells and oxidized lipoproteins, MDA-adducts serve as ligands for scavenger receptors like CD36 and SR-A1 on macrophages, triggering pro-inflammatory signaling and the formation of foam cells (Tsimikas et al., 2007). This process is a critical driver of chronic inflammatory conditions, most notably atherosclerosis and non-alcoholic steatohepatitis (NASH) (Witztum & Lichtman, 2014). Therapeutic strategies targeting MDA-modified proteins involve the use of monoclonal antibodies, such as the experimental agent ATH3149, which are designed to bind and neutralize these epitopes (Athera Biotechnologies). By blocking the interaction between MDA-adducts and immune receptors, these therapies aim to reduce vascular inflammation, stabilize atherosclerotic plaques, and prevent disease progression (Tsimikas et al., 2007).

Other names

MDA-adductsMDA-epitopesMalondialdehyde-lysine adductsOxidation-specific epitopes (OSEs)MDA-modified low-density lipoprotein (MDA-LDL)

Binding to and neutralization of pro-inflammatory oxidation-specific epitopes to inhibit macrophage activation and foam cell formation (Tsimikas et al., 2007).