IMR Press / FBL / Volume 6 / Issue 3 / DOI: 10.2741/schmidt

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Receptor for age (RAGE) is a gene within the major histocompatibility class III region: implications for host response mechanisms in homeostasis and chronic disease
Show Less
1 Departments of Surgery, College of Physicians & Surgeons, Columbia University, New York, New York 10032, USA
2 Departments of Medicine, College of Physicians & Surgeons, Columbia University, New York, New York 10032
3 Departments of Physiology & Cellular Biophysics, College of Physicians & Surgeons, Columbia University, New York, New York 10032
Front. Biosci. (Landmark Ed) 2001, 6(3), 1151–1160;
Published: 1 October 2001

Receptor for AGE (RAGE), a member of the immunoglobulin superfamily, was first identified as a specific cell surface interaction site for Advanced Glycation Endproducts, or AGEs. AGEs, the products of nonenzymatic glycation/oxidation of proteins/lipids, accumulate in natural aging and disorders such as diabetes, renal failure and amyloidoses. Interaction of AGEs with RAGE has been linked to chronic inflammatory and vascular dysfunction that characterizes the chronic complications of these disorders. Recent studies have indicated that RAGE is a multiligand receptor, serving as a specific cell surface, signal transducing receptor for amphoterin, a molecule with implications for neurite outgrowth in neuronal development and in tumor cell proliferation and spread. RAGE is also a receptor for amyloid-beta peptide, whose interaction with neuronal and microglial RAGE within the CNS is linked to sustained inflammation and neuronal toxicity and cell death. RAGE also serves as a signal-transducing receptor for EN-RAGEs, and related members of the S100/calgranulin family of proinflammatory cytokines; consequences of this interaction include initiation and propagation of inflammatory responses. Consistent with an important role for ligand-RAGE interaction in these settings, blockade of RAGE suppresses chronic cellular activation and dysfunction in murine models of diabetic complications, inflammation and tumor proliferation and metastasis. Taken together, an new paradigm is emerging which links RAGE, a gene encoded within the Major Histocompatibility Complex (MHC) Class III regions, to central host response mechanisms in homeostasis and chronic disease.

Back to top