LANP mediates neuritic pathology in Spinocerebellar ataxia type 1

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disease that results from a pathogenic glutamine-repeat expansion in the protein ataxin-1 (ATXN1). Although the functions of ATXN1 are still largely unknown, there is evidence to suggest that ATXN1 plays a role in regulating gene expression, the earliest process known to go awry in SCA1 mouse models. In this study, we show that ATXN1 reduces histone acetylation, a post-translational modification of histones associated with enhanced transcription, and represses histone acetyl transferase-mediated transcription. In addition, we find that depleting the Leucine-rich Acidic Nuclear Protein (LANP)—an ATXN1 binding inhibitor of histone acetylation—reverses aspects of SCA1 neuritic pathology.

► Spinocerebellar Ataxia Type I is a disease characterized by transcriptional derangements. ► We have identified alterations in histone acetylation. ► Depleting LANP—an ATXN1 binding inhibitor of histone acetylation—reverses aspects of SCA1 neuritic pathology.