Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disease caused by a CAG trinucleotide expansion within the SCA1-encoded protein ataxin-1. SCA1 is one of a family of nine polyglutamine diseases, including Huntington's disease. As SCA1 progresses, Purkinje cell degeneration causes cerebellar symptoms, including gait abnormalities and loss of coordination. Previous work has shown that proper cerebellar development is coordinated by RORalpha, a nuclear hormone receptor. Furthermore, RORalpha and ataxin-1 interact in vivo and share a common set of signaling targets. Purkinje cell RORalpha levels are decreased in SCA1 mice, but can be rescued by turning off ataxin-1 expression, suggesting a role for RORalpha in the prevention of SCA1 pathogenesis. This goal of this research is to determine whether loss of RORalpha exacerbates the degeneration associated with SCA1, providing new therapeutic targets for this family of neurodegenerative diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30NS055409-04
Application #
7677908
Study Section
Special Emphasis Panel (ZNS1-SRB-M (26))
Program Officer
Gwinn, Katrina
Project Start
2006-09-01
Project End
2011-08-31
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
4
Fiscal Year
2009
Total Cost
$38,771
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Neurology
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Gehrking, Kristin M; Andresen, J Michael; Duvick, Lisa et al. (2011) Partial loss of Tip60 slows mid-stage neurodegeneration in a spinocerebellar ataxia type 1 (SCA1) mouse model. Hum Mol Genet 20:2204-12