Polyglutamine diseases (PolyQ): construction and characterization of yeast models

Detalhes bibliográficos
Autor(a) principal: Dias, Patrícia Sofia Sousa
Data de Publicação: 2011
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/5642
Resumo: Dissertação apresentada para a obtenção do Grau de Mestre em Genética Molecular e Biomedicina, pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia
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spelling Polyglutamine diseases (PolyQ): construction and characterization of yeast modelsDissertação apresentada para a obtenção do Grau de Mestre em Genética Molecular e Biomedicina, pela Universidade Nova de Lisboa, Faculdade de Ciências e TecnologiaThere are a number of serious diseases which have in common the inappropriate folding of a particular protein, as polyglutamine disease group. Machado-Joseph‟s and Huntington‟s disease are grouped in the polyglutamine diseases, being the cause of the disease the presence of a CAG repeat tract in the causative gene, ATXN3 and HTT, respectively. This CAG repeats tract leads to the formation of polyglutamine tract in ataxin-3 and huntingtin proteins, respectively, that do not allow the correct protein folding. In diverse models, the expansion of the poluglutamine tract into disease related-proteins, promote their aggregation and their negative effect on cellular metabolism were described as associated to toxic effect. In this study, it was proposed the construction of the first yeast model for Machado-Joseph‟s disease and the characterization of the role of autophagy in the yeast model for Huntington‟s disease during yeast life cycle. For the yeast model for Machado-Joseph‟s disease we successfully constructed a Tet On system harboring the variant 1 genes, normal and expanded, fused with GFP gene, to further allow the subcellular localization of the expressed protein into yeast cells. In yeast model for Huntington‟s disease the chronological lifespan (CLS) of yeast cells at different physiological states after expressing the normal and the pathogenic protein and their subcellular localization, using epifluorescent microscopy was studied. It was demonstrated that cells harboring the huntingtin with 103 glutamines (pathogenic protein) during the inhibition of autophagic process, by chloroquine, presents an increased in CLS and the formation of large foci that could correspond to aggregosomes. In aged cells this effect is more pronounced leading to the hypothesis that in these cells the autophagic mechanism is impaired and enhances the toxic effects of expressed huntingtin 103Q and that the inhibition of the autophagic process can rescue the cells from the toxic effects. On the other hand, when the normal huntingtin (25Q) was expressed at exponential phase the inhibition of autophagy led to a drastic decrease on CLS, demonstrated that in functional cells the autophagy had a positive effect being a crucial process, probably removing unwanted intracellular components and providing energy.Faculdade de Ciências e TecnologiaLudovico, PaulaRUNDias, Patrícia Sofia Sousa2011-05-18T08:47:37Z20112011-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10362/5642enginfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T03:36:22Zoai:run.unl.pt:10362/5642Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:16:25.109199Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Polyglutamine diseases (PolyQ): construction and characterization of yeast models
title Polyglutamine diseases (PolyQ): construction and characterization of yeast models
spellingShingle Polyglutamine diseases (PolyQ): construction and characterization of yeast models
Dias, Patrícia Sofia Sousa
title_short Polyglutamine diseases (PolyQ): construction and characterization of yeast models
title_full Polyglutamine diseases (PolyQ): construction and characterization of yeast models
title_fullStr Polyglutamine diseases (PolyQ): construction and characterization of yeast models
title_full_unstemmed Polyglutamine diseases (PolyQ): construction and characterization of yeast models
title_sort Polyglutamine diseases (PolyQ): construction and characterization of yeast models
author Dias, Patrícia Sofia Sousa
author_facet Dias, Patrícia Sofia Sousa
author_role author
dc.contributor.none.fl_str_mv Ludovico, Paula
RUN
dc.contributor.author.fl_str_mv Dias, Patrícia Sofia Sousa
description Dissertação apresentada para a obtenção do Grau de Mestre em Genética Molecular e Biomedicina, pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia
publishDate 2011
dc.date.none.fl_str_mv 2011-05-18T08:47:37Z
2011
2011-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/5642
url http://hdl.handle.net/10362/5642
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Faculdade de Ciências e Tecnologia
publisher.none.fl_str_mv Faculdade de Ciências e Tecnologia
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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