Format

Send to

Choose Destination
See comment in PubMed Commons below
J Alzheimers Dis. 2009;16(4):833-43. doi: 10.3233/JAD-2009-1030.

RAGE and Alzheimer's disease: a progression factor for amyloid-beta-induced cellular perturbation?

Author information

1
Department of Pathology, College of Physicians & Surgeons of Columbia University, New York City, NY, USA.

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-beta peptide (Abeta) 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 Abeta-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 Abeta-induced inhibition of long-term potentiation in slices of entorhinal cortex. Increased expression of RAGE in an Abeta-rich environment, using transgenic mouse models, accelerates and accentuates pathologic, biochemical, and behavioral abnormalities compared with mice overexpressing only mutant amyloid-beta protein precursor. Interception of Abeta interaction with RAGE, by infusion of soluble RAGE, decreases Abeta content and amyloid load, as well as improving learning/memory and synaptic function, in a murine transgenic model of Abeta accumulation. These data suggest that RAGE may be a therapeutic target for AD.

PMID:
19387116
PMCID:
PMC3726270
DOI:
10.3233/JAD-2009-1030
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for IOS Press Icon for PubMed Central
    Loading ...
    Support Center