This project investigates three PD gene products, alpha-synuclein, UCH-L1 and DJ-1. The approach used is primarily that of in vitro biochemistry. The initial goal in each case is to understand the molecular basis for the effects of PD mutations or polymorphisms. Once a working hypothesis has been generated, we will design high-throughput assays that will allow us to identify drug-like molecules that reverse the effect of the mutation. These assays will be executed in core A. Finally, the working hypothesis will be tested by treating Parkinsonian Drosophila with drug-like molecules (via core B). The long-term (5 year) goal of this project is to confirm the relevance of particular targets for the treatment of PD and, possibly, to develop lead compounds for the development of new PD therapeutics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
5P50NS038375-07
Application #
7312747
Study Section
Special Emphasis Panel (ZNS1)
Project Start
Project End
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
7
Fiscal Year
2006
Total Cost
$394,293
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
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Shtifman, Alexander; Zhong, Nan; Lopez, Jose R et al. (2011) Altered Ca2+ homeostasis in the skeletal muscle of DJ-1 null mice. Neurobiol Aging 32:125-32
Vamvaca, Katherina; Lansbury Jr, Peter T; Stefanis, Leonidas (2011) N-terminal deletion does not affect ýý-synuclein membrane binding, self-association and toxicity in human neuroblastoma cells, unlike yeast. J Neurochem 119:389-97
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da Costa, Cristine Alves; Sunyach, Claire; Giaime, Emilie et al. (2009) Transcriptional repression of p53 by parkin and impairment by mutations associated with autosomal recessive juvenile Parkinson's disease. Nat Cell Biol 11:1370-5
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Cronin, Kenneth D; Ge, Dongliang; Manninger, Paul et al. (2009) Expansion of the Parkinson disease-associated SNCA-Rep1 allele upregulates human alpha-synuclein in transgenic mouse brain. Hum Mol Genet 18:3274-85

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