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http://hdl.handle.net/2445/175086
Title: | Neuron type-specific increase in lamin B1 contributes to nuclear dysfunction in Huntington's disease |
Author: | Alcalá Vida, Rafael Garcia-Forn, Marta Castany Pladevall, Carla Creus Muncunill, Jordi Ito, Yoko Blanco, Enrique Golbano, Arantxa Crespí-Vázquez, Kilian Parry, Aled Slater, Guy Samarajiwa, Shamith Peiró, Sandra Croce, Luciano Di Narita, Masashi Pérez Navarro, Esther |
Keywords: | Corea de Huntington Models animals en la investigació Huntington's chorea Animal models in research |
Issue Date: | 5-Feb-2021 |
Publisher: | EMBO Press |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.15252/emmm.202012105 |
It is part of: | EMBO Molecular Medicine, 2021, vol. 13, num. 2, p. e12105 |
URI: | http://hdl.handle.net/2445/175086 |
Related resource: | https://doi.org/10.15252/emmm.202012105 |
ISSN: | 1757-4676 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Biomedicina) |
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