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Biochem Biophys Res Commun. 2013 Sep 20;439(2):252-7. doi: 10.1016/j.bbrc.2013.08.047. Epub 2013 Aug 23.

Two β-strands of RAGE participate in the recognition and transport of amyloid-β peptide across the blood brain barrier.

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  • 1Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea.


Amyloid-β (Aβ) 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 Aβ peptide from circulating blood to human brain, and also causes the activation of the NF-κB signaling pathway. Here we show that two β-strands of RAGE participate in the interaction with Aβ peptide. Serial deletion analysis of the RAGE V domain indicates that the third and eighth β-strands are required for interaction with Aβ peptide. Site-directed mutagenesis of amino acids located in the third and eighth β-strands abolish the interaction of RAGE with Aβ peptide. Wild-type RAGE activates the NF-κB signaling pathway in response to Aβ peptide treatment, while a RAGE mutant defective in Aβ binding does not. Furthermore, use of peptide for the third β-strand or a RAGE monoclonal antibody that targets the RAGE-Aβ interaction interface inhibited transport of the Aβ 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.


Alzheimer’s disease; Aβ; RAGE; β-Strand

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