| First Author | Arancio O | Year | 2004 |
| Journal | EMBO J | Volume | 23 |
| Issue | 20 | Pages | 4096-105 |
| PubMed ID | 15457210 | Mgi Jnum | J:93305 |
| Mgi Id | MGI:3056837 | Doi | 10.1038/sj.emboj.7600415 |
| Citation | Arancio O, et al. (2004) RAGE potentiates Abeta-induced perturbation of neuronal function in transgenic mice. EMBO J 23(20):4096-105 |
| abstractText | 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. |
