Identification of a risk transcriptome and proteome in Parkinson’s disease, Dementia with Lewy bodies and rapidly progressive Dementia with Lewy bodies

[eng] Parkinson's disease (PD) is a neurodegenerative disorder characterized by movement impairment, or parkinsonism, for which there is still no cure. The manifest clinical signs result from neuronal loss of more than 60% in the substantia nigra pars compacta. Cognitive disorders and dementia...

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Autor: Garcia Esparcia, Paula
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/127141
Acceso en línea:https://hdl.handle.net/2445/127141
http://hdl.handle.net/10803/664642
Access Level:acceso abierto
Palabra clave:Malalties neurodegeneratives
Enfermedades neurodegenerativas
Malaltia de Parkinson
Demència amb cossos de Lewy
Proteòmica
Neurodegenerative Diseases
Parkinson's disease
Lewy body dementia
Proteomics
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network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Identification of a risk transcriptome and proteome in Parkinson’s disease, Dementia with Lewy bodies and rapidly progressive Dementia with Lewy bodies
title Identification of a risk transcriptome and proteome in Parkinson’s disease, Dementia with Lewy bodies and rapidly progressive Dementia with Lewy bodies
spellingShingle Identification of a risk transcriptome and proteome in Parkinson’s disease, Dementia with Lewy bodies and rapidly progressive Dementia with Lewy bodies
Garcia Esparcia, Paula
Malalties neurodegeneratives
Enfermedades neurodegenerativas
Malaltia de Parkinson
Demència amb cossos de Lewy
Proteòmica
Neurodegenerative Diseases
Parkinson's disease
Lewy body dementia
Proteomics
title_short Identification of a risk transcriptome and proteome in Parkinson’s disease, Dementia with Lewy bodies and rapidly progressive Dementia with Lewy bodies
title_full Identification of a risk transcriptome and proteome in Parkinson’s disease, Dementia with Lewy bodies and rapidly progressive Dementia with Lewy bodies
title_fullStr Identification of a risk transcriptome and proteome in Parkinson’s disease, Dementia with Lewy bodies and rapidly progressive Dementia with Lewy bodies
title_full_unstemmed Identification of a risk transcriptome and proteome in Parkinson’s disease, Dementia with Lewy bodies and rapidly progressive Dementia with Lewy bodies
title_sort Identification of a risk transcriptome and proteome in Parkinson’s disease, Dementia with Lewy bodies and rapidly progressive Dementia with Lewy bodies
dc.creator.none.fl_str_mv Garcia Esparcia, Paula
author Garcia Esparcia, Paula
author_facet Garcia Esparcia, Paula
author_role author
dc.contributor.none.fl_str_mv Ferrer, Isidro (Ferrer Abizanda)
Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental
dc.subject.none.fl_str_mv Malalties neurodegeneratives
Enfermedades neurodegenerativas
Malaltia de Parkinson
Demència amb cossos de Lewy
Proteòmica
Neurodegenerative Diseases
Parkinson's disease
Lewy body dementia
Proteomics
topic Malalties neurodegeneratives
Enfermedades neurodegenerativas
Malaltia de Parkinson
Demència amb cossos de Lewy
Proteòmica
Neurodegenerative Diseases
Parkinson's disease
Lewy body dementia
Proteomics
description [eng] Parkinson's disease (PD) is a neurodegenerative disorder characterized by movement impairment, or parkinsonism, for which there is still no cure. The manifest clinical signs result from neuronal loss of more than 60% in the substantia nigra pars compacta. Cognitive disorders and dementia in PD usually occur, thus leading to Parkinson disease with dementia (PDD). Moreover, Dementia with Lewy bodies (DLB) is also considered a neurodegenerative disease and one of the most common causes of dementia, with cognitive impairment symptoms similar to Alzheimer-type dementia, and with parkinsonism. Its onset is insidious and is characterized by a slow progression in comparison with its fast form, also known as Dementia with Lewy bodies rapidly progressive (rpDCL), which appears suddenly and progresses quickly. In these pathologies there occurs a neural degeneration not only related to the accumulation of altered proteins, but more likely as a result of multiple deleterious factors. The hypothesis of this work is that the identification of molecular changes analyzed through the application of "-omics" techniques will be useful to obtain information about a risk transcriptome/proteome in the aforementioned diseases. Thus, the main objective of the present thesis is the identification of molecular alterations underlying functional cerebral changes and anatomical modifications in different brain regions and different Braak stages of PD, as well as DCL and DCLrp, with the use of post-mortem human brain samples compared with controls, combining microarray, mRNA, protein and enzyme assays studies. The obtained results have identified molecular alterations in PD, DLB, and rpDLB of different metabolic pathways including changes in the machinery of protein synthesis, in the mitochondrial energy metabolism, in neuroinflammation, in the purine pathway, and in new signaling pathways comprising olfactory and taste receptors paths.
publishDate 2016
dc.date.none.fl_str_mv 2016
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/127141
http://hdl.handle.net/10803/664642
url https://hdl.handle.net/2445/127141
http://hdl.handle.net/10803/664642
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv (c) Garcia, 2016
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Garcia, 2016
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universitat de Barcelona
publisher.none.fl_str_mv Universitat de Barcelona
dc.source.none.fl_str_mv Tesis Doctorals - Departament - Patologia i Terapèutica Experimental
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Identification of a risk transcriptome and proteome in Parkinson’s disease, Dementia with Lewy bodies and rapidly progressive Dementia with Lewy bodiesGarcia Esparcia, PaulaMalalties neurodegenerativesEnfermedades neurodegenerativasMalaltia de ParkinsonDemència amb cossos de LewyProteòmicaNeurodegenerative DiseasesParkinson's diseaseLewy body dementiaProteomics[eng] Parkinson's disease (PD) is a neurodegenerative disorder characterized by movement impairment, or parkinsonism, for which there is still no cure. The manifest clinical signs result from neuronal loss of more than 60% in the substantia nigra pars compacta. Cognitive disorders and dementia in PD usually occur, thus leading to Parkinson disease with dementia (PDD). Moreover, Dementia with Lewy bodies (DLB) is also considered a neurodegenerative disease and one of the most common causes of dementia, with cognitive impairment symptoms similar to Alzheimer-type dementia, and with parkinsonism. Its onset is insidious and is characterized by a slow progression in comparison with its fast form, also known as Dementia with Lewy bodies rapidly progressive (rpDCL), which appears suddenly and progresses quickly. In these pathologies there occurs a neural degeneration not only related to the accumulation of altered proteins, but more likely as a result of multiple deleterious factors. The hypothesis of this work is that the identification of molecular changes analyzed through the application of "-omics" techniques will be useful to obtain information about a risk transcriptome/proteome in the aforementioned diseases. Thus, the main objective of the present thesis is the identification of molecular alterations underlying functional cerebral changes and anatomical modifications in different brain regions and different Braak stages of PD, as well as DCL and DCLrp, with the use of post-mortem human brain samples compared with controls, combining microarray, mRNA, protein and enzyme assays studies. The obtained results have identified molecular alterations in PD, DLB, and rpDLB of different metabolic pathways including changes in the machinery of protein synthesis, in the mitochondrial energy metabolism, in neuroinflammation, in the purine pathway, and in new signaling pathways comprising olfactory and taste receptors paths.[spa] La enfermedad de Parkinson (EP) es una patología neurodegenerativa perteneciente al grupo de afecciones conocidas como trastornos del movimiento, o parkinsonismo, para la cual actualmente no existe cura. Los signos clínicos que manifiesta son resultado de una pérdida neuronal superior al 60% en el área cerebral más afectada, la sustancia nigra pars compacta. Asimismo, la aparición de demencia y los desórdenes cognitivos en la EP conducen a una EP con demencia. A su vez, la Demencia con cuerpos de Lewy (DCL) es también una enfermedad neurodegenerativa considerada como una de las causas más comunes de demencia, con una sintomatología de deterioro cognitivo similar a la observable en la demencia de tipo Alzheimer y con la aparición de síntomas de parkinsonismo. Su aparición es insidiosa y se caracteriza por presentar una progresión lenta, a diferencia de su forma rápida también conocida como Demencia con cuerpos de Lewy rápidamente progresiva (DCLrp), que aparece de forma súbita y evoluciona vertiginosamente. En todas estas enfermedades se produce una degeneración neural debida no únicamente a la acumulación de proteínas alteradas, sino más probablemente consecuencia de múltiples factores deletéreos convergentes. La hipótesis de este trabajo es considerar que la identificación de cambios moleculares analizados gracias a la aplicación de métodos “-ómicos” servirá para obtener información sobre un trascriptoma/proteoma de riesgo en las anteriormente citadas enfermedades. El principal objetivo abordado en la presente tesis es la identificación de las alteraciones moleculares subyacentes a los cambios cerebrales funcionales y anatómicos presentes en diferentes regiones cerebrales y en distintos estadiajes de Braak de la EP, así como en la DCL y en la DCLrp, por medio del uso de muestras de cerebro humano post-mortem comparando con controles, combinando estudios de microarrays, mRNA, proteínas y ensayos enzimáticos. Los resultados obtenidos por medio de métodos de transcriptómica con su posterior validación y ampliación a proteómica han permitido identificar alteraciones moleculares en la EP, DCL y DCLrp de distintas vías metabólicas incluyendo cambios en la maquinaria de síntesis de proteínas, en el metabolismo mitocondrial y energético, en la neuroinflamación, en la vía de las purinas y en nuevas vías de señalización comprendiendo las vías de receptores olfatorios y gustativos.Universitat de BarcelonaFerrer, Isidro (Ferrer Abizanda)Universitat de Barcelona. Departament de Patologia i Terapèutica Experimental2016info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/127141http://hdl.handle.net/10803/664642Tesis Doctorals - Departament - Patologia i Terapèutica Experimentalreponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglés(c) Garcia, 2016info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1271412026-05-27T06:46:51Z
score 15,301603

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