An unresolved issue in the field of neurodegenerative diseases is whether exercise would have long-lasting beneficial effects or whether it would have deleterious long-term consequences by increasing the metabolic demands on already susceptible neuronal populations. Fryer et al. (see the Perspective by Gitler) now show that exercise significantly extended the life span of a mouse model for the polyglutamine neurodegenerative disorder spinocerebellar ataxia type 1 (SCA1). Exercise up-regulated epidermal growth factor, which caused down-regulation of Capicua (Cic), a transcriptional repressor that interacts with Ataxin-1 in vivo. In Cic mutant mice, all SCA1 phenotypes were rescued, including premature lethality, by reducing the level of Cic by 50%.
J. D. Fryer, P. Yu, H. Kang, C. Mandel-Brehm, A. N. Carter, J. Crespo-Barreto, Y. Gao, A. Flora, C. Shaw, H. T. Orr, H. Y. Zoghbi, Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua. Science 334, 690–693 (2011). [Abstract] [Full Text]