A Polypeptide Specifically Binds to RAGE can Alleviate the Destroy of Blood Brain-Barrier caused by Amyloid beta

Abstract

          Core tip:

• RP1 can bind to RAGE specifically in vitro.
• RP1 can effectively alleviate the destroy of TJs of blood-brain barrier and the decrease of permeability of BBB caused by Amyloid beta.
• RP1 can competitively inhibited the interaction of Amyloid beta with the RAGE in vitro, and effectively inhibit Amyloid betatransport into the brain.

  Abstract:

  Background The interaction of the receptor for advanced glycation end product (RAGE) on blood-brain-barrier (BBB) with Amyloid beta, plays an important role in the occurrence and development of AD. RP1 is a RAGE specific binding peptide, which was discovered in our previous experiments, and it has been proved to be effective on AD cell model, however, its effects on BBB tight junctions (TJs) and on Amyloid beta transport into the brain is unclear.

  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 and FD40 tests were used to confirm the stability of the BBB model, and the colocalization of the RP1 and RAGE on the 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 can effectively alleviate the destroy of TJs of BBB and the decrease of permeability of BBB caused by Amyloid beta. Furthermore, RP1 can competitively inhibit the interaction of Amyloid beta with the RAGE in vitro, and effectively inhibit Amyloid beta transport into the brain.

  Conclusion RP1 can inhibit BBB damage induced by Amyloid beta and block RAGE-Amyloid beta interaction effectively, and RP1 can be a candidate of RAGE inhibitors contributing to AD treatment.