Modulation of α-synuclein aggregation and toxicity

Detalhes bibliográficos
Autor(a) principal: Oliveira, Márcia Santos
Data de Publicação: 2013
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/11195
Resumo: Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina
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spelling Modulation of α-synuclein aggregation and toxicityα-synucleinHsp27Hsp70MethylglyoxalGlycationDissertação para obtenção do Grau de Mestre em Genética Molecular e BiomedicinaIt is widely known that α-synuclein (aSyn) is an amyloidogenic protein prone to aggregation. This protein is found in specific inclusions named Lewy bodies in the surviving neurons of Parkinsons’s disease patients and other synucleinopathy brains. This aggregation process is greatly affected by different post-translational modifications, such as phosphorylation, acetylation, and glycation. Lately it was shown that aSyn oligomeric species are more toxic than the inclusion bodies. Heat shock proteins (HSPs) are molecular chaperones able to modulate the folding and refolding of proteins. Its overexpression in Parkinson’s disease models reduces and prevents aSyn aggregation. As the reduction of aSyn aggregation can lead to an eventual accumulation of oligomeric species which may cause cell damage, the main goal of this work is to better understand the role of HSPs in aSyn oligomer formation, clarifying which are the aSyn resulting species formed in the presence of HSPs. Moreover, as glycation is suggested to accelerate abnormal protein deposition, we aimed to investigate how HSPs interfere with the oligomerization process of glycated aSyn. In this study Hsp70 seemed to induce recombinant aSyn oligomerization, generating higher molecular weight species with no associated toxicity. On the other hand, Hsp27 reduced aSyn oligomerization in vitro possibly by inducing the formation of non-reactive small oligomers. MGO glycation increased protein aggregation and cell death. Interestingly, Hsp27 overexpression reversed glycated aSyn aggregation and its associated toxicity. These results demonstrate the importance of HSPs modulation as a possible target of Parkinson’s disease therapeutics.Faculdade de Ciências e TecnologiaOuteiro, TiagoMiranda, HugoRUNOliveira, Márcia Santos20132013-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10362/11195enginfo: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:RCAAP2024-03-11T03:45:34Zoai:run.unl.pt:10362/11195Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:20:07.788996Repositório 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 Modulation of α-synuclein aggregation and toxicity
title Modulation of α-synuclein aggregation and toxicity
spellingShingle Modulation of α-synuclein aggregation and toxicity
Oliveira, Márcia Santos
α-synuclein
Hsp27
Hsp70
Methylglyoxal
Glycation
title_short Modulation of α-synuclein aggregation and toxicity
title_full Modulation of α-synuclein aggregation and toxicity
title_fullStr Modulation of α-synuclein aggregation and toxicity
title_full_unstemmed Modulation of α-synuclein aggregation and toxicity
title_sort Modulation of α-synuclein aggregation and toxicity
author Oliveira, Márcia Santos
author_facet Oliveira, Márcia Santos
author_role author
dc.contributor.none.fl_str_mv Outeiro, Tiago
Miranda, Hugo
RUN
dc.contributor.author.fl_str_mv Oliveira, Márcia Santos
dc.subject.por.fl_str_mv α-synuclein
Hsp27
Hsp70
Methylglyoxal
Glycation
topic α-synuclein
Hsp27
Hsp70
Methylglyoxal
Glycation
description Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina
publishDate 2013
dc.date.none.fl_str_mv 2013
2013-01-01T00:00:00Z
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/10362/11195
url http://hdl.handle.net/10362/11195
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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