RNAi or overexpression: Alternative therapies for Spinocerebellar Ataxia Type 1

NEUROBIOLOGY OF DISEASE

卷:56

Article

Keiser, Megan S.⁴  Geoghegan, James C.¹  Boudreau, Ryan L.¹  Lennox, Kim A.⁵  Davidson, Beverly L.^1,2,3,4 

[1] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA

[2] Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA

[3] Univ Iowa, Dept Physiol & Biophys, Iowa City, IA 52242 USA

[4] Univ Iowa, Dept Neurosci Training Program, Iowa City, IA 52242 USA

[5] Integrated DNA Technol Inc, Coralville, IA 52241 USA

关键词: Spinocerebellar Ataxia Type 1;    Ataxin-1;    Ataxin-1-like;    miRNA(-);    RNAi;    AAV;    Cerebellum;    Neurodegeneration;    Polyglutamine;   

DOI  :  10.1016/j.nbd.2013.04.003

来源: Elsevier

【 摘 要 】

Spinocerebellar Ataxia Type 1 (SCA1) is an autosomal dominant late onset neurodegenerative disease caused by an expanded polyglutamine tract in ataxin-1. Here, we compared the protective effects of overexpressing ataxin-1-like using recombinant AAVs, or reducing expression of mutant ataxin-1 using virally delivered RNA interference (RNAi), in a transgenic mouse model of SCA1. For the latter, we used an artificial microRNA (miR) design that optimizes potency, efficacy and safety to suppress ataxin-1 expression (miS1). Delivery of either ataxin-1-like or miS1 viral vectors to SCA1 mice cerebella resulted in widespread cerebellar Purkinje cell transduction and improved behavioral and histological phenotypes. Our data indicate the utility of either approach as a possible therapy for SCA1 patients. Published by Elsevier Inc.

【 授权许可】

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