Exploring motor neuron degeneration in ALS - prevention by glycoursodeoxycholic acid and signaling to microglia

Detalhes bibliográficos
Autor(a) principal: Cunha, Joana Carolina Marinho
Data de Publicação: 2012
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/12438
Resumo: Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina
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spelling Exploring motor neuron degeneration in ALS - prevention by glycoursodeoxycholic acid and signaling to microgliaSOD1 accumulationMotor neuron degenerationMitochondrial dysfunctionInflammationGUDCA protective effectsMicroglia activationDissertação para obtenção do Grau de Mestre em Genética Molecular e BiomedicinaAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects mainly motor neurons. Neuronal pathology involves glial cells, in particular microglia. However it is not known how these cells interact with motor neurons. This is particularly important because till now no therapy has shown efficacy in ALS treatment. Here, we aim (i) to evaluate the suitability of NSC-34, a hybrid cell line of neuroblastoma and motor neurons, as a model of ALS, (ii) to explore the reactivity of microglia to the neuronal released factors and (iii) to assess the efficacy of glycoursodeoxycholic acid (GUDCA), which already has shown beneficial effects in several neurodevelopmental and neurodegenerative diseases. For that, we used NSC-34 cells transfected with human superoxide dismutase 1 (hSOD1), either wild type or mutated in G93A and the microglial N9 cell line. We observed mitochondrial dysfunction, energy impairment, NO production and metalloproteinase-9 activation, with consequent apoptosis in NSC-34/hSOD1G93A cells after 4 days of differentiation, in comparison to NSC-34/hSOD1wt cells. In addition, we established GUDCA as an anti-apoptotic and anti-inflammatory agent, able to prevent all the above mentioned features. Finally, released neuronal factors induced N9 microglia apoptosis and decreased their phagocytic ability. Overall, our results emphasize NSC-34/hSOD1G93A cells as a good ALS model, highlight GUDCA as having beneficial effects and point to microglia neuroprotective failure as a determinant mechanism of ALS pathogenesis.Fundação para a Ciência e Tecnologia - PTDC/SAU-FAR/118787/2010, entitled “Are microglia a new potential target in amyotrophic lateral sclerosis (ALS)?” to DB and PEst- OE/SAU/UI4013/2011 to iMed.ULFaculdade de Ciências e TecnologiaBrites, DoraVaz, AnaRUNCunha, Joana Carolina Marinho2014-07-09T15:21:51Z20122012-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10362/12438enginfo: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:RCAAP2024-03-11T03:47:20Zoai:run.unl.pt:10362/12438Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:20:53.783257Repositório 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 Exploring motor neuron degeneration in ALS - prevention by glycoursodeoxycholic acid and signaling to microglia
title Exploring motor neuron degeneration in ALS - prevention by glycoursodeoxycholic acid and signaling to microglia
spellingShingle Exploring motor neuron degeneration in ALS - prevention by glycoursodeoxycholic acid and signaling to microglia
Cunha, Joana Carolina Marinho
SOD1 accumulation
Motor neuron degeneration
Mitochondrial dysfunction
Inflammation
GUDCA protective effects
Microglia activation
title_short Exploring motor neuron degeneration in ALS - prevention by glycoursodeoxycholic acid and signaling to microglia
title_full Exploring motor neuron degeneration in ALS - prevention by glycoursodeoxycholic acid and signaling to microglia
title_fullStr Exploring motor neuron degeneration in ALS - prevention by glycoursodeoxycholic acid and signaling to microglia
title_full_unstemmed Exploring motor neuron degeneration in ALS - prevention by glycoursodeoxycholic acid and signaling to microglia
title_sort Exploring motor neuron degeneration in ALS - prevention by glycoursodeoxycholic acid and signaling to microglia
author Cunha, Joana Carolina Marinho
author_facet Cunha, Joana Carolina Marinho
author_role author
dc.contributor.none.fl_str_mv Brites, Dora
Vaz, Ana
RUN
dc.contributor.author.fl_str_mv Cunha, Joana Carolina Marinho
dc.subject.por.fl_str_mv SOD1 accumulation
Motor neuron degeneration
Mitochondrial dysfunction
Inflammation
GUDCA protective effects
Microglia activation
topic SOD1 accumulation
Motor neuron degeneration
Mitochondrial dysfunction
Inflammation
GUDCA protective effects
Microglia activation
description Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina
publishDate 2012
dc.date.none.fl_str_mv 2012
2012-01-01T00:00:00Z
2014-07-09T15:21:51Z
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/10362/12438
url http://hdl.handle.net/10362/12438
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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