The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington's disease
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/105836 https://doi.org/10.1186/s13104-020-05053-x |
Resumo: | Objective: Compromised brain cholesterol turnover and altered regulation of brain cholesterol metabolism have been allied with some neurodegenerative diseases, including Huntington’s disease (HD). Following our previous studies in HD, in this study we aim to investigate in vitro in a neuroblastoma cellular model of HD, the effect of CYP46A1 overexpression, an essential enzyme in cholesterol metabolism, on huntingtin aggregation and levels. Results: We found that CYP46A1 reduces the quantity and size of mutant huntingtin aggregates in cells, as well as the levels of mutant huntingtin protein. Additionally, our results suggest that the observed beneficial effects of CYP46A1 in HD cells are linked to the activation of autophagy. Taken together, our results further demonstrate that CYP46A1 is a pertinent target to counteract HD progression. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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spelling |
The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington's diseaseCYP46A1CholesterolNeuroblastoma cellsHuntingtinAutophagyAnimalsCell Line, TumorCells, CulturedCholesterol 24-HydroxylaseHuntingtin ProteinHuntington DiseaseMiceMutant ProteinsAutophagyNeuroblastomaObjective: Compromised brain cholesterol turnover and altered regulation of brain cholesterol metabolism have been allied with some neurodegenerative diseases, including Huntington’s disease (HD). Following our previous studies in HD, in this study we aim to investigate in vitro in a neuroblastoma cellular model of HD, the effect of CYP46A1 overexpression, an essential enzyme in cholesterol metabolism, on huntingtin aggregation and levels. Results: We found that CYP46A1 reduces the quantity and size of mutant huntingtin aggregates in cells, as well as the levels of mutant huntingtin protein. Additionally, our results suggest that the observed beneficial effects of CYP46A1 in HD cells are linked to the activation of autophagy. Taken together, our results further demonstrate that CYP46A1 is a pertinent target to counteract HD progression.Springer Nature2020-04-10info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/105836http://hdl.handle.net/10316/105836https://doi.org/10.1186/s13104-020-05053-xeng1756-0500Nóbrega, ClévioConceição, André Francisco daCosta, Rafael GKoppenol, RebekahSequeira, Raquel LNunes, RicardoCarmo-Silva, SaraMarcelo, AdrianaMatos, Carlos A.Betuing, SandrineCaboche, JocelyneCartier, NathalieAlves, Sandroinfo: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:RCAAP2023-03-10T21:34:09Zoai:estudogeral.uc.pt:10316/105836Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:22:20.147114Repositório 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 |
The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington's disease |
title |
The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington's disease |
spellingShingle |
The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington's disease Nóbrega, Clévio CYP46A1 Cholesterol Neuroblastoma cells Huntingtin Autophagy Animals Cell Line, Tumor Cells, Cultured Cholesterol 24-Hydroxylase Huntingtin Protein Huntington Disease Mice Mutant Proteins Autophagy Neuroblastoma |
title_short |
The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington's disease |
title_full |
The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington's disease |
title_fullStr |
The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington's disease |
title_full_unstemmed |
The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington's disease |
title_sort |
The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington's disease |
author |
Nóbrega, Clévio |
author_facet |
Nóbrega, Clévio Conceição, André Francisco da Costa, Rafael G Koppenol, Rebekah Sequeira, Raquel L Nunes, Ricardo Carmo-Silva, Sara Marcelo, Adriana Matos, Carlos A. Betuing, Sandrine Caboche, Jocelyne Cartier, Nathalie Alves, Sandro |
author_role |
author |
author2 |
Conceição, André Francisco da Costa, Rafael G Koppenol, Rebekah Sequeira, Raquel L Nunes, Ricardo Carmo-Silva, Sara Marcelo, Adriana Matos, Carlos A. Betuing, Sandrine Caboche, Jocelyne Cartier, Nathalie Alves, Sandro |
author2_role |
author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Nóbrega, Clévio Conceição, André Francisco da Costa, Rafael G Koppenol, Rebekah Sequeira, Raquel L Nunes, Ricardo Carmo-Silva, Sara Marcelo, Adriana Matos, Carlos A. Betuing, Sandrine Caboche, Jocelyne Cartier, Nathalie Alves, Sandro |
dc.subject.por.fl_str_mv |
CYP46A1 Cholesterol Neuroblastoma cells Huntingtin Autophagy Animals Cell Line, Tumor Cells, Cultured Cholesterol 24-Hydroxylase Huntingtin Protein Huntington Disease Mice Mutant Proteins Autophagy Neuroblastoma |
topic |
CYP46A1 Cholesterol Neuroblastoma cells Huntingtin Autophagy Animals Cell Line, Tumor Cells, Cultured Cholesterol 24-Hydroxylase Huntingtin Protein Huntington Disease Mice Mutant Proteins Autophagy Neuroblastoma |
description |
Objective: Compromised brain cholesterol turnover and altered regulation of brain cholesterol metabolism have been allied with some neurodegenerative diseases, including Huntington’s disease (HD). Following our previous studies in HD, in this study we aim to investigate in vitro in a neuroblastoma cellular model of HD, the effect of CYP46A1 overexpression, an essential enzyme in cholesterol metabolism, on huntingtin aggregation and levels. Results: We found that CYP46A1 reduces the quantity and size of mutant huntingtin aggregates in cells, as well as the levels of mutant huntingtin protein. Additionally, our results suggest that the observed beneficial effects of CYP46A1 in HD cells are linked to the activation of autophagy. Taken together, our results further demonstrate that CYP46A1 is a pertinent target to counteract HD progression. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-04-10 |
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/10316/105836 http://hdl.handle.net/10316/105836 https://doi.org/10.1186/s13104-020-05053-x |
url |
http://hdl.handle.net/10316/105836 https://doi.org/10.1186/s13104-020-05053-x |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1756-0500 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
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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1799134112857980928 |