Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua

John D. Fryer, Peng Yu, Hyojin Kang, Caleigh Mandel-Brehm, Angela N. Carter, Juan Crespo-Barreto, Yan Gao, Adriano Flora, Chad Shaw, Harry T. Orr, Huda Y. Zoghbi

Research output: Contribution to journalArticle

84 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)690-693
Number of pages4
JournalScience
Volume334
Issue number6056
DOIs
StatePublished - Nov 4 2011

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Spinocerebellar Ataxias
Neurodegenerative Diseases
Phenotype
Poisons
Ataxia
Epidermal Growth Factor
Up-Regulation
Down-Regulation
Ataxin-1

Cite this

Fryer, J. D., Yu, P., Kang, H., Mandel-Brehm, C., Carter, A. N., Crespo-Barreto, J., ... Zoghbi, H. Y. (2011). Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua. Science, 334(6056), 690-693. https://doi.org/10.1126/science.1212673

Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua. / Fryer, John D.; Yu, Peng; Kang, Hyojin; Mandel-Brehm, Caleigh; Carter, Angela N.; Crespo-Barreto, Juan; Gao, Yan; Flora, Adriano; Shaw, Chad; Orr, Harry T.; Zoghbi, Huda Y.

In: Science, Vol. 334, No. 6056, 04.11.2011, p. 690-693.

Research output: Contribution to journalArticle

Fryer, JD, Yu, P, Kang, H, Mandel-Brehm, C, Carter, AN, Crespo-Barreto, J, Gao, Y, Flora, A, Shaw, C, Orr, HT & Zoghbi, HY 2011, 'Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua', Science, vol. 334, no. 6056, pp. 690-693. https://doi.org/10.1126/science.1212673
Fryer JD, Yu P, Kang H, Mandel-Brehm C, Carter AN, Crespo-Barreto J et al. Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua. Science. 2011 Nov 4;334(6056):690-693. https://doi.org/10.1126/science.1212673
Fryer, John D. ; Yu, Peng ; Kang, Hyojin ; Mandel-Brehm, Caleigh ; Carter, Angela N. ; Crespo-Barreto, Juan ; Gao, Yan ; Flora, Adriano ; Shaw, Chad ; Orr, Harry T. ; Zoghbi, Huda Y. / Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua. In: Science. 2011 ; Vol. 334, No. 6056. pp. 690-693.
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