Soluble receptor for advanced glycation end products: from disease marker to potential therapeutic target.
The receptor for advanced glycation end products (RAGE) is a cell-bound receptor of the immunoglobulin superfamily which may be activated by a variety of proinflammatory ligands including advanced glycoxidation end products, S100/calgranulins, high mobility group box 1, and amyloid beta-peptide. RAGE has a secretory splice isoform, soluble RAGE (sRAGE), that lacks the transmembrane domain and therefore circulates in plasma. By competing with cell-surface RAGE for ligand binding, sRAGE may contribute to the removal/neutralization of circulating ligands thus functioning as a decoy. Clinical studies have recently shown that higher plasma levels of sRAGE are associated with a reduced risk of coronary artery disease, hypertension, the metabolic syndrome, arthritis and Alzheimer's disease. Increasing the production of plasma sRAGE is therefore considered to be a promising therapeutic target that has the potential to prevent vascular damage and neurodegeneration. This review presents the state of the art in the use of sRAGE as a disease marker and discusses the therapeutic potential of targeting sRAGE for the treatment of inflammation-related diseases such as atherosclerosis, arthritis and Alzheimer's disease.
Geroldi
Diego
D
Department of Internal Medicine and Medical Therapeutics, IRCCS San Matteo Hospital, Malattie Vascolari e Metaboliche, University of Pavia, Piazzale Golgi 2, 27100 Pavia, Italy. d.geroldi@smatteo.pv.it
Falcone
Colomba
C
Emanuele
Enzo
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D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D001168:Arthritis / Q000175:diagnosis / Q000188:drug therapy; D050197:Atherosclerosis / Q000188:drug therapy; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000175:diagnosis; D003920:Diabetes Mellitus / Q000175:diagnosis; D015195:Drug Design; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000175:diagnosis; D007249:Inflammation / Q000188:drug therapy*; D008024:Ligands; D020033:Protein Isoforms; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood* / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D017127:Glycation End Products, Advanced; D008024:Ligands; D020033:Protein Isoforms; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic