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Análisis del efecto neuroprotector de agonistas de receptores nucleares en modelo farmacológico de Parkinson en neuronas dopaminérgicas.

dc.rights.licenseAtribución-NoComercial 4.0 Internacional
dc.contributor.advisorArboleda Bustos, Gonzalo Humberto
dc.contributor.advisorSandoval Hernández, Adrián Gabriel
dc.contributor.authorRodríguez Muñoz, Angela
dc.date.accessioned2020-03-04T14:59:06Z
dc.date.available2020-03-04T14:59:06Z
dc.date.issued2019-12-10
dc.identifier.citationRodriguez-Muñoz, Angela. Análisis del efecto neuroprotector de agonistas de receptores nucleares en modelo farmacológico de Parkinson en neuronas dopaminérgicas. Facultad de medicina, maestria en neurociencias. 2019.
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/75821
dc.description.abstractLa enfermedad de Parkinson (EP) es la segunda patología neurodegenerativa más prevalente a nivel mundial se caracteriza por la muerte sistemática de las neuronas de la SNpc, la cual se ha vinculado al estrés oxidativo y la difusión mitocondrial. Diferentes estudios han demostrado que la deficiencia de PINK1, una quinasa tipo serina/treonina que fosforila a AKT, causa una mayor susceptibilidad a estímulos nocivos acelerando el proceso de muerte celular. Los agonistas de receptores nucleares LXR y RXR tienen efectos neuroprotectores en modelos in vitro/ in vivo de Parkinson, sin embargo, el mecanismo por el cual ejerce dicha protección no es claro. Estudios previos han encontrado que un agonista de receptor nuclear, el GW3965, promueve un aumento en la expresión de PINK1, lo cual abre la posibilidad que este agonista de RN pueda tener un rol importante en la supervivencia neuronal, limitando el daño asociado a diversas neurotoxinas.Al mismo tiempo ha cobrado relevancia la actividad agonista de algunos extractos vegetales, como Zanthoxylum rigidum y Beilschmiedia costarricense, sobre el LXR y su posible acción neuroprotectora. El objetivo de este trabajo fue evaluar el efecto neuroprotector de agonistas de receptores nucleares, incluido los extractos vegetales, en un modelo farmacológico de Parkinson inducido con MPP+ en neuronas dopaminérgicas (CAD-SHSY5Y). Se observó un incremento significativo (p<0,001) en la supervivencia celular luego de realizar un pretratamiento con agonistas de LXR y RXR, dicha neuroprotección se asoció al incremento en p-AKT y PINK1. Al realizar el silenciamiento de PINK1 la protección previamente presentada se anula lo que demuestra la relevancia de PINK1 en la protección encontrada por el uso de agonistas de LXR y RXR. Frente al uso de extractos vegetales se encontraron resultados similares a los obtenidos con los agonistas sintéticos, sin embargo, en el caso Beilschmiedia costarricense el incremento en la expresión de PINK1 y p-AKT fue mayor a los agonistas sintéticos. Esto permite concluir que la función protectora de los agonistas de los receptores nucleares LXR y RXR puede estar asociada al incremento de PINK1 y a su vez en el aumento en la activación de la vía AKT.
dc.description.abstractParkinson's disease (PD) is the second most prevalent neurodegenerative pathology in the world characterized by the systematic death of SNpc neurons, which has been linked to oxidative stress and mitochondrial difusión. Different studies have shown that the deficiency of PINK1, a serine / threonine kinase that phosphorylates AKT, causes greater susceptibility to harmful stimuli by accelerating the process of cell death. The LXR and RXR nuclear receptor agonists have neuroprotective effects in Parkinson's in vitro / in vivo models, however, the mechanism by which it exerts such protection is unclear. Previous studies have found that a nuclear receptor agonist, the GW3965, promotes an increase in the expression of PINK1, which opens the possibility that this RN agonist may have an important role in neuronal survival, limiting the damage associated with various neurotoxins. At the same time, the agonist activity of some plant extracts, such as Zanthoxylum rigidum and Beilschmiedia costarricense, on the LXR and its possible neuroprotective action has become relevant. The objective of this work was to evaluate the neuroprotective effect of nuclear receptor agonists, including plant extracts, in a pharmacological model of Parkinson's induced with MPP + in dopaminergic neurons (CAD-SHSY5Y). A significant increase (p <0.001) in cell survival was observed after pretreatment with LXR and RXR agonists, this suggest that neuroprotection was associated with the increase in p-AKT and PINK1. When the PINK1 is silenced, the previously presented protection is annulled, which demonstrates the relevance of PINK1 in the protection found by the use of LXR and RXR agonists. Compared to the use of plant extracts, results similar to those obtained with synthetic agonists were found, however, in the case of Beilschmiedia costarricense , the increase in the expression of PINK1 and p-AKT was greater than synthetic agonists. This allows concluding that the protective function of the agonists of the nuclear receptors LXR and RXR may be associated with the increase in PINK1 and turn in the increase in the activation of the AKT pathway.
dc.format.extent108
dc.format.mimetypeapplication/pdf
dc.language.isospa
dc.rightsDerechos reservados - Universidad Nacional de Colombia
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subject.ddcMedicina y salud
dc.titleAnálisis del efecto neuroprotector de agonistas de receptores nucleares en modelo farmacológico de Parkinson en neuronas dopaminérgicas.
dc.title.alternativeAnalysis of the neuroprotector effect of nuclear receptor agonist in a pharmacological model of Parkinson disease in dopaminergic neurons
dc.typeOtro
dc.rights.spaAcceso abierto
dc.description.additionalMagíster en Neurociencias. Línea de Investigación: Enfermedades Neurodegenerativa.
dc.type.driverinfo:eu-repo/semantics/other
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.contributor.researchgroupMuerte Celular
dc.description.degreelevelMaestría
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotá
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.subject.proposalEnfermedad de Parkinson
dc.subject.proposalParkinson disease
dc.subject.proposalReceptores nucleares
dc.subject.proposalNuclear receptor
dc.subject.proposalLXR
dc.subject.proposalLXR
dc.subject.proposalRXR
dc.subject.proposalRXR
dc.subject.proposalPINK1
dc.subject.proposalPINK1
dc.type.coarhttp://purl.org/coar/resource_type/c_1843
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.contentText
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2


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Atribución-NoComercial 4.0 InternacionalEsta obra está bajo licencia internacional Creative Commons Reconocimiento-NoComercial 4.0.Este documento ha sido depositado por parte de el(los) autor(es) bajo la siguiente constancia de depósito