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Science. 2011 Nov 4;334(6056):690-3. doi: 10.1126/science.1212673.

Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua.

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  • 1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.

Abstract

Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by expansion of a translated CAG repeat in Ataxin-1 (ATXN1). To determine the long-term effects of exercise, we implemented a mild exercise regimen in a mouse model of SCA1 and found a considerable improvement in survival accompanied by up-regulation of epidermal growth factor and consequential down-regulation of Capicua, which is an ATXN1 interactor. Offspring of Capicua mutant mice bred to SCA1 mice showed significant improvement of all disease phenotypes. Although polyglutamine-expanded Atxn1 caused some loss of Capicua function, further reduction of Capicua levels--either genetically or by exercise--mitigated the disease phenotypes by dampening the toxic gain of function. Thus, exercise might have long-term beneficial effects in other ataxias and neurodegenerative diseases.

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PMID:
22053053
[PubMed - indexed for MEDLINE]
PMCID:
PMC3232424
Free PMC Article

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