Evaluación de la influencia de un grupo de metabolitos característicos de individuos con Parkinson en la función astrocítica humana mediante modelado computacional

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dc.contributor.advisorPinzón Velasco, Andrés Mauriciospa
dc.contributor.authorRojo Orozco, María Alejandraspa
dc.contributor.refereeArboleda Bustos, Gonzalo Humbertospa
dc.contributor.researchgroupGrupo de Investigación en Bioinformática y Biología de Sistemasspa
dc.date.accessioned2025-07-16T00:36:45Z
dc.date.available2025-07-16T00:36:45Z
dc.date.issued2025-07-15
dc.descriptionilustraciones, diagramasspa
dc.description.abstractEl Parkinson (EP) es una enfermedad neurodegenerativa multifactorial y poligénica, caracterizada por la acumulación de proteínas mal plegadas, como la α-sinucleína, y la pérdida de neuronas dopaminérgicas en la sustancia negra. Además, su complejidad biológica y genética aún no se comprende del todo, lo que la convierte en una de las enfermedades neurodegenerativas más prevalentes y costosas a nivel mundial. En este sentido, estudios recientes destacan el papel crucial de las células gliales, en particular los astrocitos, en enfermedades neurodegenerativas, debido a su rol en el soporte neuronal, el reciclaje de neurotransmisores, la homeostasis metabólica y la protección de la barrera hematoencefálica (BHE). Adicionalmente, también se ha evidenciado la implicación del microbioma intestinal en estos procesos mediante el eje intestino-cerebro (Gut-Brain Axis, GBA). En este contexto, el presente trabajo evalúa los efectos de metabolitos desregulados, como triptófano, indol, fructosa, ácido mirístico y ácido fenilacético, identificados en modelos computacionales del microbioma de pacientes con EP, y su impacto sobre un modelo computacional de astrocitos humanos, mediante COBRApy y análisis de balance de flujo (FBA). Se evaluaron escenarios con diferentes restricciones metabólicas, que revelaron alteraciones en rutas asociadas al metabolismo de aminoácidos esenciales y al metabolismo energético. En particular, la restricción de triptófano indujo reconfiguraciones en rutas mitocondriales, de transporte y posibles ajustes en el estado redox celular. La activación de la vía de la quinurenina (KYN) mostró un efecto compensatorio parcial al preservar flujos clave y modular rutas críticas en ausencia de triptófano. Además, se identificaron posibles cambios en la β-oxidación de lípidos, la síntesis de esteroides y el transporte lisosomal, junto con variaciones en reacciones clave P450SCC1m, NDPK6, ASPTAm y Ex_fru. Estos hallazgos subrayan el impacto potencial de metabolitos intestinales en la función astrocítica y su posible vínculo con la progresión de la EP, abriendo oportunidades para hipótesis testables y el refinamiento de modelos computacionales gliales. (Texto tomado de la fuente).spa
dc.description.abstractParkinson’s disease (PD) is a multifactorial and polygenic neurodegenerative disorder, characterized by the accumulation of misfolded proteins such as α-synuclein and the loss of dopaminergic neurons in the substantia nigra. Additionally, its biological and genetic complexity is still not fully understood, making it one of the most prevalent and costly neurodegenerative diseases worldwide. In this context, recent studies have highlighted the crucial role of glial cells—particularly astrocytes—in neurodegenerative conditions, due to their involvement in neuronal support, neurotransmitter recycling, metabolic homeostasis, and maintenance of the blood-brain barrier (BBB). Furthermore, the involvement of the intestinal microbiome in these processes has also been evidenced, mainly through the gut-brain axis (GBA).In this context, this study evaluates the effects of deregulated metabolites—such as tryptophan, indole, fructose, myristic acid, and phenylacetic acid—identified in computational microbiome models of PD patients, and their impact on a human astrocyte computational model using COBRApy and Flux Balance Analysis (FBA). We evaluated scenarios with different metabolic restrictions, which revealed alterations in pathways associated with essential amino acid metabolism and energy metabolism. In particular, tryptophan restriction induced reconfigurations in mitochondrial and transport pathways, along with potential adjustments to the cellular redox state. Activation of the kynurenine (KYN) pathway showed a partial compensatory effect by preserving key fluxes and modulating critical routes in the absence of tryptophan. Additionally, possible changes were identified in lipid β-oxidation, steroid biosynthesis, and lysosomal transport, along with variations in key reactions such as P450SCC1m, NDPK6, ASPTAm, and Ex_fru. These findings underscore the potential impact of intestinal metabolites on astrocyte function and their possible link to PD progression, opening opportunities for testable hypotheses and further refinement of glial computational models.eng
dc.description.degreelevelMaestríaspa
dc.description.degreenameMagíster en Bioinformáticaspa
dc.description.researchareaBiología de sistemasspa
dc.format.extentxiv, 96 páginasspa
dc.format.mimetypeapplication/pdfspa
dc.identifier.instnameUniversidad Nacional de Colombiaspa
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombiaspa
dc.identifier.repourlhttps://repositorio.unal.edu.co/spa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/88343
dc.language.isospaspa
dc.publisherUniversidad Nacional de Colombiaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.departmentDepartamento de Ingeniería de Sistemas e Industrialspa
dc.publisher.facultyFacultad de Ingenieríaspa
dc.publisher.placeBogotá, Colombiaspa
dc.publisher.programBogotá - Ingeniería - Maestría en Bioinformáticaspa
dc.relation.indexedBiremespa
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.licenseAtribución-NoComercial 4.0 Internacionalspa
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/spa
dc.subject.ddc610 - Medicina y salud::616 - Enfermedadesspa
dc.subject.proposalMicrobiomaspa
dc.subject.proposalAstrocitosspa
dc.subject.proposalEje intestino-cerebrospa
dc.subject.proposalParkinsonspa
dc.subject.proposalTriptófanospa
dc.subject.proposalModelado computacionalspa
dc.subject.proposalMicrobiomeeng
dc.subject.proposalAstrocyteseng
dc.subject.proposalGut-brain axiseng
dc.subject.proposalParkinson's diseaseeng
dc.subject.proposalTryptophaneng
dc.subject.proposalComputational modelingeng
dc.subject.unescoAnálisis estadísticospa
dc.subject.unescoStatistical analysiseng
dc.subject.wikidataastrocito humanospa
dc.subject.wikidatahuman astrocyteeng
dc.subject.wikidataenfermedad de Parkinsonspa
dc.subject.wikidataParkinson's diseaseeng
dc.titleEvaluación de la influencia de un grupo de metabolitos característicos de individuos con Parkinson en la función astrocítica humana mediante modelado computacionalspa
dc.title.translatedEvaluation of the influence of a group of metabolites characteristic of individuals with Parkinson’s disease on human astrocyte function through computational modelingeng
dc.typeTrabajo de grado - Maestríaspa
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dcterms.audience.professionaldevelopmentInvestigadoresspa
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oaire.accessrightshttp://purl.org/coar/access_right/c_abf2spa

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