Spinocerebellar ataxia type 1 (SCA1) is one of nine fatal inherited neurodegenerative diseases caused by expansion of an inframe CAG trinucleotide repeat. Each repeat tract encodes a stretch of glutamine residues in the affected protein, in the case of SCA1 the protein is ataxin-1 (ATXN1). Symptoms of SCA1 include loss of motor coordination and balance, slurred speech, swallowing difficulty, spasticity, and some cognitive impairment. A characteristic feature of SCA1 pathology is atrophy and eventual loss of Purkinje cells from the cerebellar cortex. Like many neurodegenerative disorders, SCA1 is typically a late onset disease suggesting that physiological changes due to aging contribute to the onset of the disease. There is currently no effective treatment. Thus, identifying signaling pathways and cellular mediators of SCA1 onset and progression remain a major challenge in the search for therapeutics and is the focus of the research outlined in this application for continued support. )

Public Health Relevance

We hypothesize that distinct cellular pathways underlie the two stages of SCA1 disease. 1) The S776/RBM17-mediated disease initiation early progression (pathogenesis), and 2) polyglutamine, age-related late progression. The long-term goal of this work is to use information obtained about these pathways to identify novel avenues for therapeutic development. )

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37NS022920-24
Application #
8228046
Study Section
Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)
Program Officer
Gwinn, Katrina
Project Start
1986-08-01
Project End
2015-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
24
Fiscal Year
2012
Total Cost
$439,434
Indirect Cost
$148,418
Name
University of Minnesota Twin Cities
Department
Pathology
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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Carlson, Kerri M; Andresen, J Michael; Orr, Harry T (2009) Emerging pathogenic pathways in the spinocerebellar ataxias. Curr Opin Genet Dev 19:247-53

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