ABSTRACT
Background The interaction of the receptor for advanced glycation end product (RAGE) on blood-brain-barrier(BBB) with amyloid β (Aβ) plays an important role in the occurrence and development of AD. RP1 is a RAGEspecific binding peptide, which was discovered in our previous experiments, and it has been proved to beeffective on AD cell model, however, its effects on BBB tight junctions (TJs) and on Aβ transport into the brain isunclear.Methods Immunofluorescence experiment was used to identify whether RP1 bound with RAGE specifically.BEnd3-immortalized mouse brain microvascular endothelial cells were used to construct a BBB model. TEER andFD40 tests were used to confirm the stability of the BBB model, and the colocalization of the RP1 and RAGE onthe surface bEnd3 cells was observed with confocal microscopy.Results We confirmed that RP1 can bind to RAGE specifically in vitro. Functional analyses indicated that RP1 caneffectively alleviate the destroy of TJs of BBB and the decrease of permeability of BBB caused by Aβ. Furthermore,RP1 can competitively inhibit the interaction of Aβ with the RAGE in vitro, and effectively inhibit Aβ transport intothe brain.Conclusion RP1 can inhibit BBB damage induced by Aβ and block RAGE-Aβ interaction effectively, and RP1 canbe a candidate of RAGE inhibitors contributing to AD treatment