In Silico Design and Verification of LAMP-BDNF Chimeric Protein for Presentation of BDNF on the Surface of Exosomes for Drug Delivery Through Blood-Brain Barrier

Abstract

Background and purpose: The mature form of brain-derived neurotrophic factor (BDNF) binds to BDNF/NT-3 growth factors receptor (Trk-B). This binding leads to activation of Ras–MAPK pathway which is integrated with cell growth and proliferation. The BDNF deficiency is correlated with various diseases and affects aging and miscellaneous. In the present study we aimed to design a chimeric LAMP-BDNF protein and assess its suitability to target neuronal cells employed in silico approaches. Materials and methods: The specific binding between the BDNF and Trk-B would be used to guide the drug loaded lysosomes in to brain tissue. So, the structure of the chimeric BDNF/LAMP2 protein was predicted and its quality was confirmed using bioinformatics tools. Then, the interaction between the structures of BDNF/LAMP2 protein and Trk-B was analyzed by protein-protein docking. The orientation of the interaction between these proteins was compared to orientation of Trk-B interaction with its specific antibody using structural superimposition. Results: Findings showed that the chimeric BDNF/LAMP2 protein could preserve the original structure of the BDNF molecule. Moreover, the chimeric BDNF/LAMP2 protein was found to be capable of interacting with Trk-B. The interaction orientation and binding affinity for BDNF/LAMP2 protein and Trk-B were similar to the orientation and binding affinity of interaction between Trk-B and its specific antibody. Conclusion: The designed chimeric BDNF/LAMP2b protein would be capable of targeting the exosomes toward neural cells and provides better drug delivery to brain tissue.

Keywords

• exosomes
• bdnf
• trk-b
• lamp2
• drug delivery