Pluto Bioinformatics

GSE139884: Huntingtons disease as a lamin B1 nuclear envelopathy

Bulk RNA sequencing

Lamins, the major structural proteins within the nuclear lamina, are crucial for the functionality of cellular nucleus and their alterations are involved in the so-called laminopathies. We previously found that Huntingtons disease (HD), a hereditary neurodegenerative disorder caused by an expansion of a CAG repeat in the huntingtin (htt) gene, courses with increased lamin B protein levels in specific brain regions in both mouse models and patients. We now show that these changes are mostly restricted to lamin B1, occur in striatal medium-sized spiny neurons and CA1 hippocampal neurons, and are accompanied by altered nuclear morphology, nucleocytoplasmic transport disruption and un-structuring of lamin-associated chromatin domains. Normalization of lamin B1 levels by betulinic acid administration in the R6/1 mouse model of HD results in beneficial restoring of nuclear lamina homeostasis and prevention of motor and cognitive dysfunction, opening a window for a new therapeutic approach for HD and other B1-type laminophaties. SOURCE: Enrique Blanco ( - Epigenetic Events in Cancer (L. Di Croce's lab) Center for Genomic Regulation (CRG)

View this experiment on Pluto Bioinformatics