Huntington’s disease as a lamin B1 nuclear envelopathy
Ontology highlight
ABSTRACT: 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 Huntington’s 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.
ORGANISM(S): Mus musculus
PROVIDER: GSE139884 | GEO | 2020/11/10
REPOSITORIES: GEO
ACCESS DATA