Exercise and Genetic Rescue of SCA1 via the Transcriptional Repressor Capicua
| Autor: | Yan Gao, Angela N. Carter, Hyojin Kang, Chad A. Shaw, Juan Crespo-Barreto, Harry T. Orr, Peng Yu, Caleigh Mandel-Brehm, Huda Y. Zoghbi, Adriano Flora, John D. Fryer |
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| Rok vydání: | 2011 |
| Předmět: |
Spinocerebellar Ataxia Type 1
Offspring Repressor Ataxin 1 Nerve Tissue Proteins Disease Bioinformatics Mice Epidermal growth factor Cerebellum medicine Animals Spinocerebellar Ataxias Gene Knock-In Techniques Nuclear protein Ataxin-1 Genetics Multidisciplinary biology Nuclear Proteins medicine.disease Mice Mutant Strains Exercise Therapy Mice Inbred C57BL Repressor Proteins Disease Models Animal Ataxins Spinocerebellar ataxia biology.protein |
| Zdroj: | Science. 334:690-693 |
| ISSN: | 1095-9203 0036-8075 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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