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- Title
RAGE potentiates Abeta-induced perturbation of neuronal function in transgenic mice.
- Authors
Arancio, Ottavio; Zhang, Hui Ping; Chen, Xi; Lin, Chang; Trinchese, Fabrizio; Puzzo, Daniela; Liu, Shumin; Hegde, Ashok; Yan, Shi Fang; Stern, Alan; Luddy, John S; Lue, Lih-Fen; Walker, Douglas G; Roher, Alex; Buttini, Manuel; Mucke, Lennart; Li, Weiying; Schmidt, Ann Marie; Kindy, Mark; Hyslop, Paul A; Stern, David M; Du Yan, Shirley Shi
- Abstract
Receptor for Advanced Glycation Endproducts (RAGE), a multiligand receptor in the immunoglobulin superfamily, functions as a signal-transducing cell surface acceptor for amyloid-beta peptide (Abeta). In view of increased neuronal expression of RAGE in Alzheimer's disease, a murine model was developed to assess the impact of RAGE in an Abeta-rich environment, employing transgenics (Tgs) with targeted neuronal overexpression of RAGE and mutant amyloid precursor protein (APP). Double Tgs (mutant APP (mAPP)/RAGE) displayed early abnormalities in spatial learning/memory, accompanied by altered activation of markers of synaptic plasticity and exaggerated neuropathologic findings, before such changes were found in mAPP mice. In contrast, Tg mice bearing a dominant-negative RAGE construct targeted to neurons crossed with mAPP animals displayed preservation of spatial learning/memory and diminished neuropathologic changes. These data indicate that RAGE is a cofactor for Abeta-induced neuronal perturbation in a model of Alzheimer's-type pathology, and suggest its potential as a therapeutic target to ameliorate cellular dysfunction.
- Publication
The EMBO journal, 2004, Vol 23, Issue 20, p4096
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1038/sj.emboj.7600415