The role of RAGE in amyloid-beta peptide-mediated pathology in Alzheimer's disease.
This review discusses current knowledge of the complex interactions between amyloid-beta (A beta) peptide, the receptor for advanced glycation endproducts (RAGE), and inflammatory mediators, focusing on the roles of such interactions in the pathogenesis of Alzheimer's disease. As a ubiquitous cell-surface receptor, RAGE demonstrates enhanced expression in an A beta-rich environment; the effects of RAGE on microglia, the blood-brain barrier and neurons are mediated through various signaling pathways. Relevant preclinical models illustrate that the A beta-RAGE interaction amplifies neuronal stress and the accumulation of A beta, impairs memory and learning, and exaggerates neuroinflammation. These findings suggest that RAGE may mediate a common proinflammatory pathway in neurodegenerative disorders.
Schmidt
Ann Marie
AM
Columbia University, College of Physicians and Surgeons, Department of Surgery, 630 West 168th Street, P&S 17-401, New York, NY 10032, USA. ams11@columbia.edu
Sahagan
Barbara
B
Nelson
Robert B
RB
Selmer
Johan
J
Rothlein
Robert
R
Bell
Joanne M
JM
D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D051379:Mice; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000819:agonists / Q000502:physiology*
D016229:Amyloid beta-Peptides; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic