Evaluación in silico de toxinas peptídicas de origen animal con efecto antagonista sobre la actividad del Receptor - N-Metil-D-Aspatarto (NMDA)
The N-methyl-D-aspartate receptor (NMDAR) constitutes the main subtype of glutamate receptors, involved in physiological processes such as neuronal development, transmission and synaptic plasticity, and in numerous pathological conditions such as ischemic damage, chronic pain, psychosis, and other d...
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| Formato: | Tesis y disertaciones (Maestría y/o Doctorado) |
| Lenguaje: | spa |
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Universidad Antonio Nariño
2021
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| Acceso en línea: | http://repositorio.uan.edu.co/handle/123456789/5036 |
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| _version_ | 1812647916998754304 |
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| author | Gamboa Rodríguez, Katherin Alejandra |
| author2 | Reyes Guzman, Edwin Alfredo |
| author_facet | Reyes Guzman, Edwin Alfredo Gamboa Rodríguez, Katherin Alejandra |
| author_sort | Gamboa Rodríguez, Katherin Alejandra |
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| description | The N-methyl-D-aspartate receptor (NMDAR) constitutes the main subtype of glutamate
receptors, involved in physiological processes such as neuronal development, transmission
and synaptic plasticity, and in numerous pathological conditions such as ischemic damage,
chronic pain, psychosis, and other degenerative disorders. The NMDAR has a structural
topology consisting of four subunits mainly of the GluN1 and GluN2(A-B) type. The
ionotropic NMDAR corresponds to an ionic-cation channel, permeable mainly to calcium
ion. An excessive increase in calcium influx via NMDAR generates excitotoxicity which
translates into neuronal damage and death. Based on the above, it is essential to search for
molecules that generate interaction with the receptor and specifically with the GluN2B
subunit, modulate the activity of the receptor-channel and can be recycled or eliminated by
the organism. The present thesis proposal proposes the design and in silico characterization
of peptides derived from animal toxins with potential targeting of the NMDAR.
The design included the use of computational analysis tools, alignments and docking and
molecular dynamics simulations, which allowed predicting the three-dimensional structure
of a series of peptide toxins and proposing peptides derived from them as potential NMDAR
ligands |
| format | Tesis y disertaciones (Maestría y/o Doctorado) |
| id | repositorio.uan.edu.co-123456789-5036 |
| institution | Repositorio Digital UAN |
| language | spa |
| publishDate | 2021 |
| publisher | Universidad Antonio Nariño |
| record_format | dspace |
| spelling | repositorio.uan.edu.co-123456789-50362024-10-09T23:05:37Z Evaluación in silico de toxinas peptídicas de origen animal con efecto antagonista sobre la actividad del Receptor - N-Metil-D-Aspatarto (NMDA) Gamboa Rodríguez, Katherin Alejandra Reyes Guzman, Edwin Alfredo Forero Vivas, María Elisa NMDA toxinas péptido excitotoxicidad bioinformática calcio intracelular NMDA toxins peptide excitotoxicity bioinformatics intracellular calcium The N-methyl-D-aspartate receptor (NMDAR) constitutes the main subtype of glutamate receptors, involved in physiological processes such as neuronal development, transmission and synaptic plasticity, and in numerous pathological conditions such as ischemic damage, chronic pain, psychosis, and other degenerative disorders. The NMDAR has a structural topology consisting of four subunits mainly of the GluN1 and GluN2(A-B) type. The ionotropic NMDAR corresponds to an ionic-cation channel, permeable mainly to calcium ion. An excessive increase in calcium influx via NMDAR generates excitotoxicity which translates into neuronal damage and death. Based on the above, it is essential to search for molecules that generate interaction with the receptor and specifically with the GluN2B subunit, modulate the activity of the receptor-channel and can be recycled or eliminated by the organism. The present thesis proposal proposes the design and in silico characterization of peptides derived from animal toxins with potential targeting of the NMDAR. The design included the use of computational analysis tools, alignments and docking and molecular dynamics simulations, which allowed predicting the three-dimensional structure of a series of peptide toxins and proposing peptides derived from them as potential NMDAR ligands El receptor N-Metil-D-Aspartato (NMDAR) constituye el principal subtipo de receptores de glutamato, implicado en procesos fisiológicos como desarrollo neuronal, transmisión y plasticidad sináptica, y en numerosas condiciones patológicas como el daño isquémico, dolor crónico, psicosis, y otros trastornos degenerativos. El NMDAR presenta una topología estructural conformada por cuatro subunidades principalmente de tipo GluN1 y GluN2(AB). El NMDAR ionotrópico corresponde a un canal iónico-catiónico, permeable principalmente al ion calcio. Un aumento excesivo del influjo de calcio vía NMDAR genera excitotoxicidad la cual se traduce en daño y muerte neuronal. Con base en lo anterior se hace indispensable la búsqueda de moléculas que generen interacción con el receptor y específicamente con la subunidad GluN2B, modulen la actividad del receptor-canal y puedan ser reciclados o eliminados por el organismo. La presente propuesta de tesis plantea el diseño y caracterización in silico de péptidos derivados de toxinas de origen animal como potencial blanco el NMDAR. El diseño incluyó el uso de herramientas computacionales de análisis, alineamientos y simulaciones de docking y dinámica molecular, lo que permitió predecir la estructura tridimensional de una serie de toxinas peptídicas y proponer péptidos derivados de estas como posibles ligandos del NMDAR Magíster en Bioquímica Maestría Presencial 2021-10-14T16:03:04Z 2021-10-14T16:03:04Z 2021-06-23 Tesis y disertaciones (Maestría y/o Doctorado) info:eu-repo/semantics/acceptedVersion http://purl.org/coar/resource_type/c_bdcc http://purl.org/coar/version/c_970fb48d4fbd8a85 http://repositorio.uan.edu.co/handle/123456789/5036 Aizenman, E., Frosch, M. P., & Lipton, S. A. (1988). Responses mediated by excitatory amino acid receptors in solitary retinal ganglion cells from rat. The Journal of Physiology, 396(1), 75–91. https://doi.org/10.1113/jphysiol.1988.sp016951 Asztély, F., & Gustafsson, B. (1996). Ionotropic glutamate receptors: Their possible role in the expression of hippocampal synaptic plasticity. Molecular Neurobiology, 12(1), 1– 11. https://doi.org/10.1007/BF02740744 Bianchi, R., Wong, R. K. S., & Merlin, L. R. (2013). Glutamate Receptors in Epilepsy. Jasper’s Basic Mechanisms of the Epilepsies, 116, 132–142. https://doi.org/10.1093/med/9780199746545.003.0011 Bleich, S., Römer, K., Wiltfang, J., & Kornhuber, J. (2003). Glutamate and the glutamate receptor system: A target for drug action. International Journal of Geriatric Psychiatry, 18(SUPPL. 1). https://doi.org/10.1002/gps.933 Bliss, T. V. ., & Collingridge, G. L. (1993). A synaptic mechanism of memory: ling term potantiation in the hippocampus. Group. Bowery, N. G., & Smart, T. G. (2006). GABA and glycine as neurotransmitters: A brief history. British Journal of Pharmacology, 147(SUPPL. 1), 109–119. https://doi.org/10.1038/sj.bjp.0706443 Bradley, P., Misura, K. M. S., & Baker, D. (2005). Toward High-Resolution de Novo 53 Structure Prediction for Small Proteins. Science, 309(5742), 1868 LP – 1871. https://doi.org/10.1126/science.1113801 Brosnan, J. T. (2018). Glutamate, at the Interface between Amino Acid and Carbohydrate Metabolism. The Journal of Nutrition, 130(4), 988S-990S. https://doi.org/10.1093/jn/130.4.988s de Souza, J. M., Goncalves, B. D. C., Gomez, M. V., Vieira, L. B., & Ribeiro, F. M. (2018). Animal toxins as therapeutic tools to treat neurodegenerative diseases. Frontiers in Pharmacology, 9(FEB), 1–25. https://doi.org/10.3389/fphar.2018.00145 de Lima M.E. et al. (2016) Phoneutria nigriventer Venom and Toxins: A Review. In: Gopalakrishnakone P., Corzo G., de Lima M., Diego-García E. (eds) Spider Venoms. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6389-0_6. Doctoral, T. (n.d.). Mecanismos de regulación del receptor de glutamato tipo NMDA en excitotoxicidad e isquemia cerebral. Dunnett, S. B., & Björklund, A. (1999). Prospects for new restorative and neuroprotective treatments in Parkinson’s disease. Nature, 399(SUPPL.). https://doi.org/10.1038/399a032 F. Traynelis, S., P. Wollmuth, L., J. McBain, C., S. Menniti, F., M. Vance, K., K. Ogden, K., … Dingledine, R. (2010). Glutamate Receptor Ion Channels: Structure, Regulation, and Function Stephen. Pharmacological Reviews, 62, 405–496. https://doi.org/10.1124/pr.109.002451.405 instname:Universidad Antonio Nariño reponame:Repositorio Institucional UAN repourl:https://repositorio.uan.edu.co/ spa Acceso abierto Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) https://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess http://purl.org/coar/access_right/c_abf2 application/pdf application/pdf application/pdf Universidad Antonio Nariño Maestría en Bioquímica Facultad de Ciencias Bogotá - Circunvalar |
| spellingShingle | NMDA toxinas péptido excitotoxicidad bioinformática calcio intracelular NMDA toxins peptide excitotoxicity bioinformatics intracellular calcium Gamboa Rodríguez, Katherin Alejandra Evaluación in silico de toxinas peptídicas de origen animal con efecto antagonista sobre la actividad del Receptor - N-Metil-D-Aspatarto (NMDA) |
| title | Evaluación in silico de toxinas peptídicas de origen animal con efecto antagonista sobre la actividad del Receptor - N-Metil-D-Aspatarto (NMDA) |
| title_full | Evaluación in silico de toxinas peptídicas de origen animal con efecto antagonista sobre la actividad del Receptor - N-Metil-D-Aspatarto (NMDA) |
| title_fullStr | Evaluación in silico de toxinas peptídicas de origen animal con efecto antagonista sobre la actividad del Receptor - N-Metil-D-Aspatarto (NMDA) |
| title_full_unstemmed | Evaluación in silico de toxinas peptídicas de origen animal con efecto antagonista sobre la actividad del Receptor - N-Metil-D-Aspatarto (NMDA) |
| title_short | Evaluación in silico de toxinas peptídicas de origen animal con efecto antagonista sobre la actividad del Receptor - N-Metil-D-Aspatarto (NMDA) |
| title_sort | evaluacion in silico de toxinas peptidicas de origen animal con efecto antagonista sobre la actividad del receptor n metil d aspatarto nmda |
| topic | NMDA toxinas péptido excitotoxicidad bioinformática calcio intracelular NMDA toxins peptide excitotoxicity bioinformatics intracellular calcium |
| url | http://repositorio.uan.edu.co/handle/123456789/5036 |
| work_keys_str_mv | AT gamboarodriguezkatherinalejandra evaluacioninsilicodetoxinaspeptidicasdeorigenanimalconefectoantagonistasobrelaactividaddelreceptornmetildaspatartonmda |
