Advanced glycation end product-specific receptor (RAGE) (RAGE)

The Advanced glycation end product-specific receptor (RAGE) is a multi-ligand transmembrane receptor belonging to the immunoglobulin superfamily (UniProt Q15109). It plays a central role in the pathological effects of advanced glycation end products (AGEs), which are proteins or lipids that become non-enzymatically glycated after exposure to sugars (PubMed 23533503). The binding of AGEs to RAGE triggers pro-inflammatory signaling pathways, including the activation of NF-κB, leading to oxidative stress and chronic inflammation (PubMed 19085579). This pathway is heavily implicated in the pathogenesis of diabetic complications, cardiovascular disease, and neurodegenerative conditions like Alzheimer's disease (PubMed 22503560). Therapeutic strategies aimed at modulating AGE metabolism include RAGE antagonists like azeliragon, AGE formation inhibitors such as aminoguanidine, and cross-link breakers like alagebrium (PubMed 18446170, PubMed 11739991). Despite their potential, many of these agents have faced challenges in clinical trials due to insufficient efficacy or safety concerns (PubMed 29674266).

Other names

AGERReceptor for advanced glycation end productsAdvanced glycosylation end product-specific receptor

Modulation of AGE metabolism involves inhibiting the non-enzymatic glycation of proteins, breaking established AGE cross-links, or antagonizing the RAGE receptor to block downstream pro-inflammatory signaling (PubMed 23533503, PubMed 18446170).