Exploring the molecular mechanisms of the human VGF-derived antidepressant neuropeptide TLQp-62 on neurogenesis

VGF-derived neuropeptide TLQP-62 has antidepressant-like properties by increasing hippocampal neurogenesis. This process and VGF levels were found to be impaired in neuropsychiatric disorders. In the present study TLQP-62 was found to promote neurodifferentiation of the human SH-SY5Y cell line by en...

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Autor: Moutinho, Daniela Mesquita
Tipo de recurso: tesis doctoral
Fecha de publicación:2019
País:España
Institución:Universidad de Santiago de Compostela (USC)
Repositorio:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
Idioma:inglés
OAI Identifier:oai:minerva.usc.gal:10347/18376
Acceso en línea:http://hdl.handle.net/10347/18376
Access Level:acceso abierto
Palabra clave:Materias::Investigación::24 Ciencias de la vida::2407 Biología celular::240703 Morfología celular
Materias::Investigación::24 Ciencias de la vida::2490 Neurociencias::249001 Neurofisiología
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spelling Exploring the molecular mechanisms of the human VGF-derived antidepressant neuropeptide TLQp-62 on neurogenesisMoutinho, Daniela MesquitaMaterias::Investigación::24 Ciencias de la vida::2407 Biología celular::240703 Morfología celularMaterias::Investigación::24 Ciencias de la vida::2490 Neurociencias::249001 NeurofisiologíaVGF-derived neuropeptide TLQP-62 has antidepressant-like properties by increasing hippocampal neurogenesis. This process and VGF levels were found to be impaired in neuropsychiatric disorders. In the present study TLQP-62 was found to promote neurodifferentiation of the human SH-SY5Y cell line by enhancing the expression of several proteins involved in cell cycle regulation, in oxidative stress, in energy metabolism and biosynthesis, and in cytoskeletal organization, promoting neurite outgrowth. All those processes contribute to neurodevelopment and synaptic function. Human TLQP-62 receptor was identified as the G-protein coupled receptor OR5P3, promoting an increase in cAMP levels to initiate signal transduction. TLQP-62 was also found to bind the HSPA8 chaperone. This neuropeptide 3D structure was also found to be mainly disordered but to be transitory with a C-term α-helix that might be stabilized by HSPA8 contributing to its receptor binding and activation. All together these data can contribute to the development of a possible TLQP-62 receptor agonist to be used as a therapy for some neuropsychiatric disorders.Rodríguez Requena, JesúsUniversidade de Santiago de Compostela. Centro Internacional de Estudos de Doutoramento e Avanzados (CIEDUS)Universidade de Santiago de Compostela. Escola de Doutoramento Internacional en Ciencias da Saúde20192019-01-0120192019-01-01doctoral thesishttp://purl.org/coar/resource_type/c_db06info:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/10347/18376reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostelainstname:Universidad de Santiago de Compostela (USC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:minerva.usc.gal:10347/183762026-06-15T12:47:27Z
dc.title.none.fl_str_mv Exploring the molecular mechanisms of the human VGF-derived antidepressant neuropeptide TLQp-62 on neurogenesis
title Exploring the molecular mechanisms of the human VGF-derived antidepressant neuropeptide TLQp-62 on neurogenesis
spellingShingle Exploring the molecular mechanisms of the human VGF-derived antidepressant neuropeptide TLQp-62 on neurogenesis
Moutinho, Daniela Mesquita
Materias::Investigación::24 Ciencias de la vida::2407 Biología celular::240703 Morfología celular
Materias::Investigación::24 Ciencias de la vida::2490 Neurociencias::249001 Neurofisiología
title_short Exploring the molecular mechanisms of the human VGF-derived antidepressant neuropeptide TLQp-62 on neurogenesis
title_full Exploring the molecular mechanisms of the human VGF-derived antidepressant neuropeptide TLQp-62 on neurogenesis
title_fullStr Exploring the molecular mechanisms of the human VGF-derived antidepressant neuropeptide TLQp-62 on neurogenesis
title_full_unstemmed Exploring the molecular mechanisms of the human VGF-derived antidepressant neuropeptide TLQp-62 on neurogenesis
title_sort Exploring the molecular mechanisms of the human VGF-derived antidepressant neuropeptide TLQp-62 on neurogenesis
dc.creator.none.fl_str_mv Moutinho, Daniela Mesquita
author Moutinho, Daniela Mesquita
author_facet Moutinho, Daniela Mesquita
author_role author
dc.contributor.none.fl_str_mv Rodríguez Requena, Jesús
Universidade de Santiago de Compostela. Centro Internacional de Estudos de Doutoramento e Avanzados (CIEDUS)
Universidade de Santiago de Compostela. Escola de Doutoramento Internacional en Ciencias da Saúde
dc.subject.none.fl_str_mv Materias::Investigación::24 Ciencias de la vida::2407 Biología celular::240703 Morfología celular
Materias::Investigación::24 Ciencias de la vida::2490 Neurociencias::249001 Neurofisiología
topic Materias::Investigación::24 Ciencias de la vida::2407 Biología celular::240703 Morfología celular
Materias::Investigación::24 Ciencias de la vida::2490 Neurociencias::249001 Neurofisiología
description VGF-derived neuropeptide TLQP-62 has antidepressant-like properties by increasing hippocampal neurogenesis. This process and VGF levels were found to be impaired in neuropsychiatric disorders. In the present study TLQP-62 was found to promote neurodifferentiation of the human SH-SY5Y cell line by enhancing the expression of several proteins involved in cell cycle regulation, in oxidative stress, in energy metabolism and biosynthesis, and in cytoskeletal organization, promoting neurite outgrowth. All those processes contribute to neurodevelopment and synaptic function. Human TLQP-62 receptor was identified as the G-protein coupled receptor OR5P3, promoting an increase in cAMP levels to initiate signal transduction. TLQP-62 was also found to bind the HSPA8 chaperone. This neuropeptide 3D structure was also found to be mainly disordered but to be transitory with a C-term α-helix that might be stabilized by HSPA8 contributing to its receptor binding and activation. All together these data can contribute to the development of a possible TLQP-62 receptor agonist to be used as a therapy for some neuropsychiatric disorders.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-01-01
2019
2019-01-01
dc.type.none.fl_str_mv doctoral thesis
http://purl.org/coar/resource_type/c_db06
dc.type.openaire.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
dc.identifier.none.fl_str_mv http://hdl.handle.net/10347/18376
url http://hdl.handle.net/10347/18376
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
instname:Universidad de Santiago de Compostela (USC)
instname_str Universidad de Santiago de Compostela (USC)
reponame_str Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
collection Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
repository.name.fl_str_mv
repository.mail.fl_str_mv
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