Receptor for AGE (RAGE): signaling mechanisms in the pathogenesis of diabetes and its complications.
The receptor for advanced glycation endproducts (RAGE) was first described as a signal transduction receptor for advanced glycation endproducts (AGEs), the products of nonenzymatic glycation and oxidation of proteins and lipids that accumulate in diabetes and in inflammatory foci. The discovery that RAGE was a receptor for inflammatory S100/calgranulins and high mobility group box 1 (HMGB1) set the stage for linking RAGE to both the consequences and causes of types 1 and 2 diabetes. Recent discoveries regarding the structure of RAGE as well as novel intracellular binding partner interactions advance our understanding of the mechanisms by which RAGE evokes pathological consequences and underscore strategies by which antagonism of RAGE in the clinic may be realized. Finally, recent data tracking RAGE in the clinic suggest that levels of soluble RAGEs and polymorphisms in the gene encoding RAGE may hold promise for the identification of patients who are vulnerable to the complications of diabetes and/or are receptive to therapeutic interventions designed to prevent and reverse the damage inflicted by chronic hyperglycemia, irrespective of its etiology.
Diabetes Research Program, Division of Endocrinology, Department of Medicine, New York University School of Medicine, New York, New York 10016, USA.
Ravichandran
R
Ramasamy
Shi Fang
SF
Yan
Ann Marie
AM
Schmidt
D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D048909:Diabetes Complications / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D003920:Diabetes Mellitus / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism; D000080865:Formins; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D051379:Mice; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D002352:Carrier Proteins; C491464:Diap1 protein, mouse; D000080865:Formins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic