Journal article
RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia
Nature medicine, Vol.10(8), pp.816-820
08/01/2004
DOI: 10.1038/nm1076
PMID: 15235598
Abstract
The dominant polyglutamine expansion diseases, which include spinocerebellar ataxia type 1 (SCA1) and Huntington disease, are progressive, untreatable, neurodegenerative disorders. In inducible mouse models of SCA1 and Huntington disease, repression of mutant allele expression improves disease phenotypes. Thus, therapies designed to inhibit expression of the mutant gene would be beneficial. Here we evaluate the ability of RNA interference (RNAi) to inhibit polyglutamine-induced neurodegeneration caused by mutant ataxin-1 in a mouse model of SCA1. Upon intracerebellar injection, recombinant adeno-associated virus (AAV) vectors expressing short hairpin RNAs profoundly improved motor coordination, restored cerebellar morphology and resolved characteristic ataxin-1 inclusions in Purkinje cells of SCA1 mice. Our data demonstrate in vivo the potential use of RNAi as therapy for dominant neurodegenerative disease.
Details
- Title: Subtitle
- RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia
- Creators
- Haibin Xia - University of IowaQinwen Mao - University of IowaSteven L Eliason - University of IowaScott Q Harper - University of IowaInês H Martins - University of IowaHarry T Orr - University of MinnesotaHenry L Paulson - University of IowaLinda Yang - National Heart Lung and Blood InstituteRobert M Kotin - National Heart Lung and Blood InstituteBeverly L Davidson - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Nature medicine, Vol.10(8), pp.816-820
- DOI
- 10.1038/nm1076
- PMID
- 15235598
- ISSN
- 1078-8956
- eISSN
- 1546-170X
- Language
- English
- Date published
- 08/01/2004
- Academic Unit
- Anatomy and Cell Biology; Internal Medicine
- Record Identifier
- 9984622757302771
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