| First Author | Kim SJ | Year | 2013 |
| Journal | Biochem Biophys Res Commun | Volume | 439 |
| Issue | 2 | Pages | 252-7 |
| PubMed ID | 23973487 | Mgi Jnum | J:211371 |
| Mgi Id | MGI:5574557 | Doi | 10.1016/j.bbrc.2013.08.047 |
| Citation | Kim SJ, et al. (2013) Two beta-strands of RAGE participate in the recognition and transport of amyloid-beta peptide across the blood brain barrier. Biochem Biophys Res Commun 439(2):252-7 |
| abstractText | Amyloid-beta (Abeta) peptide is central to the development of brain pathology in Alzheimer disease (AD) patients. Association with receptors for advanced glycation end-products (RAGE) enables the transport of Abeta peptide from circulating blood to human brain, and also causes the activation of the NF-kappaB signaling pathway. Here we show that two beta-strands of RAGE participate in the interaction with Abeta peptide. Serial deletion analysis of the RAGE V domain indicates that the third and eighth beta-strands are required for interaction with Abeta peptide. Site-directed mutagenesis of amino acids located in the third and eighth beta-strands abolish the interaction of RAGE with Abeta peptide. Wild-type RAGE activates the NF-kappaB signaling pathway in response to Abeta peptide treatment, while a RAGE mutant defective in Abeta binding does not. Furthermore, use of peptide for the third beta-strand or a RAGE monoclonal antibody that targets the RAGE-Abeta interaction interface inhibited transport of the Abeta peptide across the blood brain barrier in a mice model. These results provide information crucial to the development of RAGE-derived therapeutic reagents for Alzheimer disease. |
