Glycation reaction and the role of the receptor for advanced glycation end-products in immunity and social behavior

Dual Nature of RAGE in Host Reaction and Nurturing the Mother–Infant Bond

“…Apart from AGEs, RAGE is known to interact with a series of different ligands, including high-mobility group box-1 (HMGB1), Gram-negative bacterial cell wall lipopolysaccharides (LPS), S100 proteins, complement component C3, phosphatidylserine (PS), and amyloid-β. The chemical structures of AGEs include N ε -carboxy-methyl-lysine (CML), N ε -carboxy-ethyl-lysine (CEL), glyceraldehyde-derived pyridinium (GLAP), glycolaldehyde (GA)-pyridine, pentosidine, and methylglyoxal-derived hydroimidazolone 1 (MG-H1) [2,5,8,16,19,20]. The CMLmodified S100A8/A9 strongly activates intestinal inflammatory responses via RAGE, which suggests that complex varieties of RAGE ligands are modified by glycation reactions [21].…”

“…RAGE has an extracellular (V, C1, and C2 domains) region, a transmembrane region, and a short cytoplasmic tail (ctRAGE) of 43 amino acids with a high charge [2,5]. For signal transduction, ctRAGE required an adaptor protein, diaphanous-related formin 1 (Diaph1), which led to the phosphorylation of its downstream effector protein Rac1, an essential factor for cell movement in rat C6 glioma cells [22].…”

“…It has been reported that approximately 10% of dietary AGEs are absorbed after oral ingestion and then assimilated into the circulation via the human gastrointestinal tract [3]. AGEs can induce intrinsic cell signaling pathways and, in turn, contribute to the development of various diseases via the receptor for AGEs (RAGE) on cell membranes [2,4,5].…”

“…Anti-aging treatments have attracted increasing attention in recent years, focusing on anti-glycation to reduce morbidity, ensure healthier aging and longevity, and promote cosmetic enhancement. Targeting RAGE could be a preventive and therapeutic strategy against various RAGE-associated diseases, including inflammatory disorders, diabetes mellitus and its complications, aging-related diseases, neurodegenerative disorders, and cancer growth and metastasis [2,[4][5][6][7][8][9][10][11][12][13][14][15][16].…”

“…RAGE is a multiligand pattern-recognition receptor belonging to the immunoglobulin superfamily [4][5][6]. We recently discovered that RAGE present on brain vascular endothelial cells can bind oxytocin (OT) and transport it from the blood to the brain, resulting in the regulation of brain OT levels.…”