Advanced glycosylation end product-specific receptor (RAGE)

The Advanced glycosylation end product-specific receptor (RAGE) is a multiligand transmembrane receptor belonging to the immunoglobulin superfamily that acts as a pattern recognition receptor [1, 2]. It binds a diverse array of ligands, including advanced glycation end-products (AGEs), high mobility group box 1 (HMGB1), S100/calgranulin proteins, and amyloid-beta peptides [3, 5]. Upon ligand binding, RAGE initiates complex intracellular signaling cascades, primarily through the activation of NF-kappaB, which leads to the sustained production of pro-inflammatory cytokines and reactive oxygen species [1, 17]. While expressed at low levels in most healthy tissues, RAGE is significantly upregulated in chronic inflammatory environments, playing a pivotal role in the pathogenesis of diabetic complications, cardiovascular diseases, neurodegeneration, and cancer progression [2, 11, 18]. Therapeutic strategies targeting RAGE include small-molecule antagonists like Azeliragon and decoy receptors like soluble RAGE (sRAGE), which aim to block ligand-receptor interactions or disrupt intracellular signaling to mitigate chronic inflammation [2, 10, 13].

Other names

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

Antagonist of ligand binding to the extracellular domain or inhibition of intracellular signaling by blocking adaptor protein interactions.