Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/108907
DC FieldValueLanguage
dc.contributor.authorOnofre, Isabel-
dc.contributor.authorMendonça, Nuno-
dc.contributor.authorLopes, Sara-
dc.contributor.authorNobre, Rui J.-
dc.contributor.authorMelo, Joana Barbosa-
dc.contributor.authorCarreira, Isabel Marques-
dc.contributor.authorJanuário, Cristina-
dc.contributor.authorGonçalves, António Freire-
dc.contributor.authorAlmeida, Luís Pereira de-
dc.date.accessioned2023-09-25T07:57:38Z-
dc.date.available2023-09-25T07:57:38Z-
dc.date.issued2016-06-22-
dc.identifier.issn2045-2322pt
dc.identifier.urihttps://hdl.handle.net/10316/108907-
dc.description.abstractMachado Joseph Disease (MJD) is the most frequent autosomal dominantly inherited cerebellar ataxia caused by the over-repetition of a CAG trinucleotide in the ATXN3 gene. This expansion translates into a polyglutamine tract within the ataxin-3 protein that confers a toxic gain-of-function to the mutant protein ataxin-3, contributing to protein misfolding and intracellular accumulation of aggregates and neuronal degeneration. Autophagy impairment has been shown to be one of the mechanisms that contribute for the MJD phenotype. Here we investigated whether this phenotype was present in patient-derived fibroblasts, a common somatic cell type used in the derivation of induced pluripotent stem cells and subsequent differentiation into neurons, for in vitro disease modeling. We generated and studied adult dermal fibroblasts from 5 MJD patients and 4 healthy individuals and we found that early passage MJD fibroblasts exhibited autophagy impairment with an underlying mechanism of decreased autophagosome production. The overexpression of beclin-1 on MJD fibroblasts reverted partially autophagy impairment by increasing the autophagic flux but failed to increase the levels of autophagosome production. Overall, our results provide a well-characterized MJD fibroblast resource for neurodegenerative disease research and contribute for the understanding of mutant ataxin-3 biology and its molecular consequences.pt
dc.language.isoengpt
dc.publisherSpringer Naturept
dc.relationCENTRO-07-ST24-FEDER-002006pt
dc.relationPTDC/SAU-NMC/116512/2010)pt
dc.relationEuropean Spinocerebellar Ataxia Type 3/Machado-Joseph Disease Initiative, ModelPolyQpt
dc.relationSynSpread, under the JPND-Joint Programme on Neurodegenerative Diseasept
dc.relationRichard Chin and Lily Lock Machado Joseph Disease Research Fundpt
dc.relationNational Ataxia Foundation.pt
dc.relationSFRH/BD/61461/2009pt
dc.relationSFRH/BD/51673/2011pt
dc.relationSFRH/BPD/66705/2009pt
dc.rightsopenAccesspt
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt
dc.subject.meshAtaxin-3pt
dc.subject.meshAutophagosomespt
dc.subject.meshBeclin-1pt
dc.subject.meshCells, Culturedpt
dc.subject.meshDNApt
dc.subject.meshFibroblastspt
dc.subject.meshGenetic Vectorspt
dc.subject.meshGenotypept
dc.subject.meshHumanspt
dc.subject.meshKaryotypept
dc.subject.meshMachado-Joseph Diseasept
dc.subject.meshMicrotubule-Associated Proteinspt
dc.subject.meshSequestosome-1 Proteinpt
dc.subject.meshAutophagypt
dc.titleFibroblasts of Machado Joseph Disease patients reveal autophagy impairmentpt
dc.typearticle-
degois.publication.firstPage28220pt
degois.publication.issue1pt
degois.publication.titleScientific Reportspt
dc.peerreviewedyespt
dc.identifier.doi10.1038/srep28220pt
degois.publication.volume6pt
dc.date.embargo2016-06-22*
uc.date.periodoEmbargo0pt
item.languageiso639-1en-
item.openairetypearticle-
item.grantfulltextopen-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextCom Texto completo-
item.cerifentitytypePublications-
crisitem.author.deptFaculty of Medicine-
crisitem.author.parentdeptUniversity of Coimbra-
crisitem.author.researchunitMARE - Marine and Environmental Sciences Centre-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCIBB - Center for Innovative Biomedicine and Biotechnology-
crisitem.author.orcid0000-0002-4937-448X-
crisitem.author.orcid0000-0002-5567-282X-
crisitem.author.orcid0000-0002-4322-8529-
crisitem.author.orcid0000-0001-5816-2051-
crisitem.author.orcid0000-0001-5049-2670-
crisitem.author.orcid0000-0001-6842-1707-
crisitem.author.orcid0000-0001-5402-3978-
crisitem.author.orcid0000-0001-5831-3307-
Appears in Collections:IIIUC - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais
FFUC- Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais
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