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
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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Mazandaran University of Medical Sciences
2022-12-01
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| Series: | Journal of Mazandaran University of Medical Sciences |
| Subjects: | |
| Online Access: | http://jmums.mazums.ac.ir/article-1-17695-en.html |
| _version_ | 1797893155656302592 |
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| author | Saeed Khalili Seyedeh Farzaneh Mahdavian Niloufar Ahmadifard Reza Valadan Naghi Shahabi Majd Hosein Ranjbaran Mohammad Reza Mahdavi Atena Sharif Razavi Shabanali Khodashenas |
| author_facet | Saeed Khalili Seyedeh Farzaneh Mahdavian Niloufar Ahmadifard Reza Valadan Naghi Shahabi Majd Hosein Ranjbaran Mohammad Reza Mahdavi Atena Sharif Razavi Shabanali Khodashenas |
| author_sort | Saeed Khalili |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T06:48:25Z |
| format | Article |
| id | doaj.art-749a93072fef4a3d8a7e50fba0988198 |
| institution | Directory Open Access Journal |
| issn | 1735-9260 1735-9279 |
| language | English |
| last_indexed | 2024-04-10T06:48:25Z |
| publishDate | 2022-12-01 |
| publisher | Mazandaran University of Medical Sciences |
| record_format | Article |
| series | Journal of Mazandaran University of Medical Sciences |
| spelling | doaj.art-749a93072fef4a3d8a7e50fba09881982023-02-28T09:18:48ZengMazandaran University of Medical SciencesJournal of Mazandaran University of Medical Sciences1735-92601735-92792022-12-01322154961In Silico Design and Verification of LAMP-BDNF Chimeric Protein for Presentation of BDNF on the Surface of Exosomes for Drug Delivery Through Blood-Brain BarrierSaeed Khalili0Seyedeh Farzaneh Mahdavian1Niloufar Ahmadifard2Reza Valadan3Naghi Shahabi Majd4Hosein Ranjbaran5Mohammad Reza Mahdavi6Atena Sharif Razavi7Shabanali Khodashenas8 Assistant Professor, Department of Biological Sciences, Shahid Rajaee Teacher Training University, Tehran, Iran MSc Student in Medical Biotechnology, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran MSc Student in Medical Biotechnology, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran Assistant Professor, Department of Immunology, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran Assistant Professor, Department of Immunology, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran 4Assistant Professor, Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran Assistant Professor, Department of Laboratory Sciences, Faculty of Allied Medical Sciences, Mazandaran University of Medical Sciences, Sari, Iran.Thalassemia Research Center, Mazandaran University of Medical Sciences, Sari, Iran Assistant Professor, Department of Neurology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Assistant Professor, Department of Medical Biotechnology, Faculty of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran 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.http://jmums.mazums.ac.ir/article-1-17695-en.htmlexosomesbdnftrk-blamp2drug delivery |
| spellingShingle | Saeed Khalili Seyedeh Farzaneh Mahdavian Niloufar Ahmadifard Reza Valadan Naghi Shahabi Majd Hosein Ranjbaran Mohammad Reza Mahdavi Atena Sharif Razavi Shabanali Khodashenas 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 Journal of Mazandaran University of Medical Sciences exosomes bdnf trk-b lamp2 drug delivery |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | exosomes bdnf trk-b lamp2 drug delivery |
| url | http://jmums.mazums.ac.ir/article-1-17695-en.html |
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