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RAGE and Alzheimer’s Disease: A Progression Factor for Amyloid-β-Induced Cellular Perturbation?
Yan, Shirley ShiDu Bierhaus, Angelika Nawroth, Peter P. Stern, David M.
Yan, Shirley ShiDu
Bierhaus, Angelika
Nawroth, Peter P.
Stern, David M.
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Abstract
Receptor for Advanced Glycation Endproducts (RAGE) is a multiligand member of the immunoglobulin superfamily of cell surface molecules which serves as a receptor for amyloid-β peptide (Aβ) on neurons, microglia, astrocytes, and cells of vessel wall. Increased expression of RAGE is observed in regions of the brain affected by Alzheimer's disease (AD), and Aβ-RAGE interaction in vitro leads to cell stress with the generation of reactive oxygen species and activation of downstream signaling mechanisms including the MAP kinase pathway. RAGE-mediated activation of p38 MAP kinase in neurons causes Aβ-induced inhibition of long-term potentiation in slices of entorhinal cortex. Increased expression of RAGE in an Aβ-rich environment, using transgenic mouse models, accelerates and accentuates pathologic, biochemical, and behavioral abnormalities compared with mice overexpressing only mutant amyloid-β protein precursor. Interception of Aβ interaction with RAGE, by infusion of soluble RAGE, decreases Aβ content and amyloid load, as well as improving learning/memory and synaptic function, in a murine transgenic model of Aβ accumulation. These data suggest that RAGE may be a therapeutic target for AD.
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This is the publisher's version, also available electronically from http://iospress.metapress.com/content/d6621608n32478r2/?genre=article&issn=1387-2877&volume=16&issue=4&spage=833
Date
2009-04
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IOS Press
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Yan_et_al_April2009.pdf
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Amyloid-β peptide receptor, Cerebral blood flow, endothelin-1, Immunoglobulin superfamily, Long-term potentiation, transgenic model
Citation
Yan, Shirley ShiDu et al. (2009). RAGE and Alzheimer’s Disease: A Progression Factor for Amyloid-β-Induced Cellular Perturbation? Journal of Alzheimer's Disease 16(4):833-843.