Blockade of receptor for advanced glycation endproducts: a new target for therapeutic intervention in diabetic complications and inflammatory disorders.
The glycation and oxidation of proteins/lipids leads to the generation of a new class of biologically active moieties, the advanced glycation endproducts (AGEs). Recent studies have elucidated that carboxymethyllysine (CML) adducts of proteins/lipids are a highly prevalent AGE in vivo. CML-modified adducts are signal transduction ligands of the receptor for AGE (RAGE), a member of the immunoglobulin superfamily. Importantly, CML-modified adducts accumulate in diverse settings. In addition to enhanced formation in settings of high glucose, these adducts form in inflammatory milieu. Studies performed both in vitro and in vivo have suggested that the proinflammatory/tissue destructive consequences of RAGE activation in the diabetic/inflamed environment may be markedly attenuated by blockade of the ligand-RAGE axis. Here, we will summarize the known consequences of RAGE activation in the tissues and highlight novel areas for therapeutic intervention in these disease states.
Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. bh2021@columbia.edu
Barry I
BI
Hudson
Loredana G
LG
Bucciarelli
Thoralf
T
Wendt
Taichi
T
Sakaguchi
Evanthia
E
Lalla
Wu
W
Qu
Yan
Y
Lu
Larisse
L
Lee
David M
DM
Stern
Yoshifumi
Y
Naka
Ravichandran
R
Ramasamy
Shi Du
SD
Yan
Shi Fang
SF
Yan
Vivette
V
D'Agati
Ann Marie
AM
Schmidt
D000818:Animals; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism*; D005544:Forecasting; D014644:Genetic Variation; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D007249:Inflammation / Q000150:complications / Q000378:metabolism*; D008024:Ligands; D008954:Models, Biological; D010084:Oxidation-Reduction; D011110:Polymorphism, Genetic; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D017127:Glycation End Products, Advanced; D007136:Immunoglobulins; D008024:Ligands; D011971:Receptors, Immunologic