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http://hdl.handle.net/2445/175086
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DC Field | Value | Language |
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dc.contributor.author | Alcalá Vida, Rafael | - |
dc.contributor.author | Garcia-Forn, Marta | - |
dc.contributor.author | Castany Pladevall, Carla | - |
dc.contributor.author | Creus Muncunill, Jordi | - |
dc.contributor.author | Ito, Yoko | - |
dc.contributor.author | Blanco, Enrique | - |
dc.contributor.author | Golbano, Arantxa | - |
dc.contributor.author | Crespí-Vázquez, Kilian | - |
dc.contributor.author | Parry, Aled | - |
dc.contributor.author | Slater, Guy | - |
dc.contributor.author | Samarajiwa, Shamith | - |
dc.contributor.author | Peiró, Sandra | - |
dc.contributor.author | Croce, Luciano Di | - |
dc.contributor.author | Narita, Masashi | - |
dc.contributor.author | Pérez Navarro, Esther | - |
dc.date.accessioned | 2021-03-15T15:20:28Z | - |
dc.date.available | 2021-03-15T15:20:28Z | - |
dc.date.issued | 2021-02-05 | - |
dc.identifier.issn | 1757-4676 | - |
dc.identifier.uri | http://hdl.handle.net/2445/175086 | - |
dc.description.abstract | Lamins are crucial proteins for nuclear functionality. Here, we provide new evidence showing that increased lamin B1 levels contribute to the pathophysiology of Huntington's disease (HD), a CAG repeat-associated neurodegenerative disorder. Through fluorescence-activated nuclear suspension imaging, we show that nucleus from striatal medium-sized spiny and CA1 hippocampal neurons display increased lamin B1 levels, in correlation with altered nuclear morphology and nucleocytoplasmic transport disruption. Moreover, ChIP-sequencing analysis shows an alteration of lamin-associated chromatin domains in hippocampal nuclei, accompanied by changes in chromatin accessibility and transcriptional dysregulation. Supporting lamin B1 alterations as a causal role in mutant huntingtin-mediated neurodegeneration, pharmacological normalization of lamin B1 levels in the hippocampus of the R6/1 mouse model of HD by betulinic acid administration restored nuclear homeostasis and prevented motor and cognitive dysfunction. Collectively, our work points increased lamin B1 levels as a new pathogenic mechanism in HD and provides a novel target for its intervention. | - |
dc.format.extent | 25 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | EMBO Press | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.15252/emmm.202012105 | - |
dc.relation.ispartof | EMBO Molecular Medicine, 2021, vol. 13, num. 2, p. e12105 | - |
dc.relation.uri | https://doi.org/10.15252/emmm.202012105 | - |
dc.rights | cc-by (c) Alcalá Vida, Rafael et al., 2021 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
dc.source | Articles publicats en revistes (Biomedicina) | - |
dc.subject.classification | Corea de Huntington | - |
dc.subject.classification | Models animals en la investigació | - |
dc.subject.other | Huntington's chorea | - |
dc.subject.other | Animal models in research | - |
dc.title | Neuron type-specific increase in lamin B1 contributes to nuclear dysfunction in Huntington's disease | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 708537 | - |
dc.date.updated | 2021-03-15T15:20:28Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 33369245 | - |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Biomedicina) |
Files in This Item:
File | Description | Size | Format | |
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708537.pdf | 10.4 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License