Journal article
RNAi or overexpression: Alternative therapies for Spinocerebellar Ataxia Type 1
Neurobiology of disease, Vol.56, pp.6-13
08/2013
DOI: 10.1016/j.nbd.2013.04.003
PMCID: PMC4173078
PMID: 23583610
Abstract
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.
•AAV-expressed human ataxin-1-like improves behavior and histology in SCA1 mice.•Ataxin-1-like interacts with mutant ataxin-1 in vivo.•Prolonged reduction of ataxin-1 via artificial miRNAs rescues SCA1 phenotypes.
Details
- Title: Subtitle
- RNAi or overexpression: Alternative therapies for Spinocerebellar Ataxia Type 1
- Creators
- Megan S Keiser - Department of the Neuroscience Training Program, University of Iowa, Iowa City, IA 52242, USAJames C Geoghegan - Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USARyan L Boudreau - Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USAKim A Lennox - Integrated DNA Technologies Inc., Coralville, IA 52241, USABeverly L Davidson - Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Neurobiology of disease, Vol.56, pp.6-13
- DOI
- 10.1016/j.nbd.2013.04.003
- PMID
- 23583610
- PMCID
- PMC4173078
- NLM abbreviation
- Neurobiol Dis
- ISSN
- 0969-9961
- eISSN
- 1095-953X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 08/2013
- Academic Unit
- Iowa Neuroscience Institute; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984065387902771
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