Copy-number variation of the neuronal glucose transporter gene SLC2A3 and age of onset in Huntington's disease

Detalhes bibliográficos
Autor(a) principal: Vittori, Angelica
Data de Publicação: 2014
Outros Autores: Breda, Carlo, Repici, Mariaelena, Orth, Michael, Roos, Raymund A. C., Outeiro, Tiago, Giorgini, Flaviano, Hollox, Edward J.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/51217
Resumo: © The Author 2014. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
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spelling Copy-number variation of the neuronal glucose transporter gene SLC2A3 and age of onset in Huntington's diseasePhenotypeGlucose metabolismHuntington's disease© The Author 2014. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Huntington's disease (HD) is a devastating neurodegenerative disorder which is inherited in an autosomal dominant manner. HD is caused by a trinucleotide CAG repeat expansion that encodes a polyglutamine stretch in the huntingtin (HTT) protein. Mutant HTT expression leads to a myriad of cellular dysfunctions culminating in neuronal loss and consequent motor, cognitive and psychiatric disturbances in HD patients. The length of the CAG repeat is inversely correlated with age of onset (AO) in HD patients, while environmental and genetic factors can further modulate this parameter. Here, we explored whether the recently described copy-number variation (CNV) of the gene SLC2A3-which encodes the neuronal glucose transporter GLUT3-could modulate AO in HD. Strikingly, we found that increased dosage of SLC2A3 delayed AO in an HD cohort of 987 individuals, and that this correlated with increased levels of GLUT3 in HD patient cells. To our knowledge this is the first time that CNV of a candidate gene has been found to modulate HD pathogenesis. Furthermore, we found that increasing dosage of Glut1-the Drosophila melanogaster homologue of this glucose transporter-ameliorated HD-relevant phenotypes in fruit flies, including neurodegeneration and life expectancy. As alterations in glucose metabolism have been implicated in HD pathogenesis, this study may have important therapeutic relevance for HD.A.V. was supported by a FCT PhD studentship (SFRH/BD/4764/2008) awarded to T.F.O., F.G. and E.J.H. Both E.J.H. and F.G. were supported by MRC New Investigator awards (GO801123 to E.J.H. and G0700090 to F.G.). T.F.O. is supported by the DFG Center of Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB).Oxford University PressRepositório da Universidade de LisboaVittori, AngelicaBreda, CarloRepici, MariaelenaOrth, MichaelRoos, Raymund A. C.Outeiro, TiagoGiorgini, FlavianoHollox, Edward J.2022-02-10T17:10:33Z20142014-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/51217engHum Mol Genet. 2014 Jun 15;23(12):3129-31370964-690610.1093/hmg/ddu0221460-2083info: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:RCAAP2023-11-08T16:55:46Zoai:repositorio.ul.pt:10451/51217Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:02:32.808994Repositório 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 Copy-number variation of the neuronal glucose transporter gene SLC2A3 and age of onset in Huntington's disease
title Copy-number variation of the neuronal glucose transporter gene SLC2A3 and age of onset in Huntington's disease
spellingShingle Copy-number variation of the neuronal glucose transporter gene SLC2A3 and age of onset in Huntington's disease
Vittori, Angelica
Phenotype
Glucose metabolism
Huntington's disease
title_short Copy-number variation of the neuronal glucose transporter gene SLC2A3 and age of onset in Huntington's disease
title_full Copy-number variation of the neuronal glucose transporter gene SLC2A3 and age of onset in Huntington's disease
title_fullStr Copy-number variation of the neuronal glucose transporter gene SLC2A3 and age of onset in Huntington's disease
title_full_unstemmed Copy-number variation of the neuronal glucose transporter gene SLC2A3 and age of onset in Huntington's disease
title_sort Copy-number variation of the neuronal glucose transporter gene SLC2A3 and age of onset in Huntington's disease
author Vittori, Angelica
author_facet Vittori, Angelica
Breda, Carlo
Repici, Mariaelena
Orth, Michael
Roos, Raymund A. C.
Outeiro, Tiago
Giorgini, Flaviano
Hollox, Edward J.
author_role author
author2 Breda, Carlo
Repici, Mariaelena
Orth, Michael
Roos, Raymund A. C.
Outeiro, Tiago
Giorgini, Flaviano
Hollox, Edward J.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Vittori, Angelica
Breda, Carlo
Repici, Mariaelena
Orth, Michael
Roos, Raymund A. C.
Outeiro, Tiago
Giorgini, Flaviano
Hollox, Edward J.
dc.subject.por.fl_str_mv Phenotype
Glucose metabolism
Huntington's disease
topic Phenotype
Glucose metabolism
Huntington's disease
description © The Author 2014. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
publishDate 2014
dc.date.none.fl_str_mv 2014
2014-01-01T00:00:00Z
2022-02-10T17:10:33Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/51217
url http://hdl.handle.net/10451/51217
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Hum Mol Genet. 2014 Jun 15;23(12):3129-3137
0964-6906
10.1093/hmg/ddu022
1460-2083
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 Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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
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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
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