LANP mediates neuritic pathology in Spinocerebellar ataxia type 1

• Main Authors: Marija Cvetanovic, Rupinder K. Kular, Puneet Opal
• Format: Article
• Language: English
• Published: Elsevier 2012-12-01
• Series: Neurobiology of Disease
• Subjects: LANP; pp32; ANP32-A; Spinocerebellar ataxia type 1; SCA1; Neurite outgrowth
• Online Access: http://www.sciencedirect.com/science/article/pii/S0969996112002744

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.