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LANP mediates neuritic pathology in Spinocerebellar ataxia type 1.

ABSTRACT: 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.

SUBMITTER: Cvetanovic M

PROVIDER: S-EPMC3987943 | biostudies-other | 2012 Dec

REPOSITORIES: biostudies-other

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LANP mediates neuritic pathology in Spinocerebellar ataxia type 1.

Cvetanovic Marija M Kular Rupinder K RK Opal Puneet P

Neurobiology of disease 20120804 3

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 associate ...[more]

PMID: 22884877

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