Advanced glycation end-products (AGEs) formation (AGE formation)

Advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed through the non-enzymatic reaction between reducing sugars and the amino groups of proteins, lipids, or nucleic acids, known as the Maillard reaction (Singh et al., 2014, Korean J Physiol Pharmacol). This process is significantly accelerated under conditions of hyperglycemia and oxidative stress, leading to the production of reactive dicarbonyl intermediates like methylglyoxal (Vlassara & Uribarri, 2014, Curr Diab Rep). The accumulation of AGEs results in the irreversible cross-linking of long-lived proteins such as collagen, which increases tissue stiffness and impairs organ function (Goldin et al., 2006, Circulation). Furthermore, AGEs interact with the Receptor for AGEs (RAGE) to trigger pro-inflammatory and pro-oxidative signaling pathways that contribute to the pathogenesis of diabetic nephropathy, retinopathy, and atherosclerosis (Ahmed, 2005, Diabetes Res Clin Pract). Therapeutic strategies targeting this process include the use of AGE inhibitors that scavenge reactive precursors or "AGE breakers" designed to cleave existing protein cross-links (Bolton et al., 2004, Expert Opin Ther Targets). Despite their potential, many candidates have faced challenges in clinical development due to safety concerns, such as the inhibition of essential vitamin B6-dependent enzymes.

Other names

Maillard reactionNon-enzymatic glycosylationProtein glycationGlycation processNon-enzymatic protein browning

Inhibition of reactive carbonyl species (RCS) formation, scavenging of dicarbonyl intermediates such as methylglyoxal, and chemical cleavage of established alpha-diketone protein cross-links (Ahmed, 2005, Diabetes Res Clin Pract).