title: Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua.
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.
authors: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors: John D
authors: JD
authors: Fryer
authors: Peng
authors: P
authors: Yu
authors: Hyojin
authors: H
authors: Kang
authors: Caleigh
authors: C
authors: Mandel-Brehm
authors: Angela N
authors: AN
authors: Carter
authors: Juan
authors: J
authors: Crespo-Barreto
authors: Yan
authors: Y
authors: Gao
authors: Adriano
authors: A
authors: Flora
authors: Chad
authors: C
authors: Shaw
authors: Harry T
authors: HT
authors: Orr
authors: Huda Y
authors: HY
authors: Zoghbi
mesh_terms: D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D002531:Cerebellum / Q000378:metabolism; D004195:Disease Models, Animal; D005081:Exercise Therapy; D055879:Gene Knock-In Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D020754:Spinocerebellar Ataxias / Q000235:genetics / Q000628:therapy*
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; C498611:Cic protein, mouse; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins