| Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua. | |
| | |
MedLine Citation:
|
PMID: 22053053 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
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 |
Related Documents
:
|
9172053 - Effects of maternal exercise on fetal activity in late gestation. 1306643 - Infant acceptance of postexercise breast milk. 12659013 - Biochemical and hematological responses of the banded knife fish gymnotus carapo (linna... |
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: 2012-05-07 |
Medline Journal Info:
|
Nlm Unique ID: 0404511 Medline TA: Science Country: United States |
Other Details:
|
Languages: eng Pagination: 690-3 Citation Subset: IM |
Affiliation:
|
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cerebellum / metabolism Disease Models, Animal Exercise Therapy* Gene Knock-In Techniques Mice Mice, Inbred C57BL Mice, Mutant Strains Nerve Tissue Proteins / genetics Nuclear Proteins / genetics Repressor Proteins / genetics, physiology* Spinocerebellar Ataxias / genetics, therapy* |
| Grant Support | |
ID/Acronym/Agency:
|
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 HD024064-22/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 |
| Chemical | |
Reg. No./Substance:
|
0/Cic protein, mouse; 0/Nerve Tissue Proteins; 0/Nuclear Proteins; 0/Repressor Proteins; 0/ataxin-1 |
| Comments/Corrections | |
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
Previous Document: Drosophila CENH3 is sufficient for centromere formation.
Next Document: Social network size affects neural circuits in macaques.