Receptor for advanced glycation end-products (RAGE) is a cell surface transmembrane multi-ligand receptor belonging to the immunoglobulin superfamily, encoded by the AGER gene.

The link between the RAGE and its multiple ligands, including Glycation End Product (AGEs) triggers a cascade of intracellular events and transcription of genes, as well as other reactions such as the formation of oxidative stress. These reactions are involved in neurological and vascular complications of diabetes, Alzheimer's Disease, arthritis, and some cancers. In addition, chronic stimulation of RAGE triggers different signaling pathways and reactions^1,2.

RAGE is a 35 kDa protein mainly expressed in the lungs and exists under two main forms: membrane-bound RAGE (mRAGE) and soluble RAGE (sRAGE). Membrane-bound RAGE has three domains: an extracellular domain that recognizes and binds RAGE ligands, a hydrophobic transmembrane domain, and a charged cytoplasmic domain that functions in intracellular signaling. Soluble RAGE contains only the extracellular domain and is a product of either alternative splicing events or the proteolytic cleavage of mRAGE. Because it can bind ligands but cannot transduce signals intracellularly, sRAGE is a decoy receptor that sequesters RAGE ligands and prevents inflammatory responses³.

Use of sRAGE, RAGE blocking antibody, or a small molecule inhibitors to interfere with RAGE signaling may become novel therapeutic approaches to inhibit RAGE-mediated disease⁴.