The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington’s disease

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 c...

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Autores principales: Nóbrega, Clévio, Conceição, André, 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Research Note
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149904/
https://www.ncbi.nlm.nih.gov/pubmed/32276655
http://dx.doi.org/10.1186/s13104-020-05053-x
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author Nóbrega, Clévio
Conceição, André
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_facet Nóbrega, Clévio
Conceição, André
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_sort Nóbrega, Clévio
collection PubMed
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.
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spelling pubmed-71499042020-04-19 The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington’s disease Nóbrega, Clévio Conceição, André 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 BMC Res Notes Research Note 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. BioMed Central 2020-04-10 /pmc/articles/PMC7149904/ /pubmed/32276655 http://dx.doi.org/10.1186/s13104-020-05053-x Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Note
Nóbrega, Clévio
Conceição, André
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
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
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_short The cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of Huntington’s disease
title_sort cholesterol 24-hydroxylase activates autophagy and decreases mutant huntingtin build-up in a neuroblastoma culture model of huntington’s disease
topic Research Note
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149904/
https://www.ncbi.nlm.nih.gov/pubmed/32276655
http://dx.doi.org/10.1186/s13104-020-05053-x
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