# name
Neuron type-specific increase in lamin B1 contributes to nuclear dysfunction in Huntington's disease

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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.

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EMBO Molecular Medicine, 2021, vol. 13, num. 2, p. e12105

# metadata.dc.rights[].value
cc-by (c) Alcalá Vida, Rafael et al., 2021

# metadata.dc.source[].value
Articles publicats en revistes (Biomedicina)

# metadata.dc.title[].value
Neuron type-specific increase in lamin B1 contributes to nuclear dysfunction in Huntington's disease