Document Detail

Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua.
MedLine Citation:
PMID:  22053053     Owner:  NLM     Status:  MEDLINE    
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.
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
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Publication Detail:
Type:  Journal Article; Research Support, American Recovery and Reinvestment Act; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  334     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-04     Completed Date:  2012-01-25     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  690-3     Citation Subset:  IM    
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MeSH Terms
Cerebellum / metabolism
Disease Models, Animal
Exercise Therapy*
Gene Knock-In Techniques
Mice, Inbred C57BL
Mice, Mutant Strains
Nerve Tissue Proteins / genetics
Nuclear Proteins / genetics
Repressor Proteins / genetics,  physiology*
Spinocerebellar Ataxias / genetics,  therapy*
Grant Support
1F32NS055545/NS/NINDS NIH HHS; HD24064/HD/NICHD NIH HHS; NS022920/NS/NINDS NIH HHS; NS045667/NS/NINDS NIH HHS; NS27699/NS/NINDS NIH HHS; NS27699-20S1/NS/NINDS NIH HHS; P30 HD024064/HD/NICHD NIH HHS; P30 HD024064-22/HD/NICHD NIH HHS; P30 HD024064-23/HD/NICHD NIH HHS; R01 NS027699/NS/NINDS NIH HHS; R01 NS027699-20S1/NS/NINDS NIH HHS; R01 NS027699-21/NS/NINDS NIH HHS; R01 NS027699-22/NS/NINDS NIH HHS; //Howard Hughes Medical Institute; //Howard Hughes Medical Institute
Reg. No./Substance:
0/Cic protein, mouse; 0/Nerve Tissue Proteins; 0/Nuclear Proteins; 0/Repressor Proteins; 0/ataxin-1
Comment In:
Science. 2011 Nov 4;334(6056):606-7   [PMID:  22053033 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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