Abstract

Core A brings the technology and expertise of modern robotic drug discovery to bear on the scientific problems ofthe BWH Udall Center. This technology will be used to find drug-like molecules that target proteins and processes relevant to PD. The effect of these molecules on the neurodegenerative process in Parkinsonian Drosophila mice, or neurons will provide important information about the relationship between the target and PD. This approach, called chemical genetics, is not widely available to the academic community because of the significant barriers with respect to personnel and equipment costs. This core will support the execution of screens generated by BWH Udall investigators, in the Harvard Laboratory for Drug Discovery in Neurodegeneration. In addition, the core will disseminate results of those screens, including interesting bioactive compounds, to all of the Udall Centers. Finally, the core will provide training to visiting scientists Iron:, other Udall centers.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
5P50NS038375-10
Application #
7932143
Study Section
Special Emphasis Panel (ZNS1)
Project Start
Project End
Budget Start
2009-09-01
Budget End
2010-08-31
Support Year
10
Fiscal Year
2009
Total Cost
$108,663
Indirect Cost

  Institution

Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Bartels, Tim; Choi, Joanna G; Selkoe, Dennis J (2011) ýý-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation. Nature 477:107-10
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
Berger, Zdenek; Smith, Kelsey A; Lavoie, Matthew J (2010) Membrane localization of LRRK2 is associated with increased formation of the highly active LRRK2 dimer and changes in its phosphorylation. Biochemistry 49:5511-23
Giaime, E; Sunyach, C; Druon, C et al. (2010) Loss of function of DJ-1 triggered by Parkinson's disease-associated mutation is due to proteolytic resistance to caspase-6. Cell Death Differ 17:158-69
Logan, Todd; Clark, Lindsay; Ray, Soumya S (2010) Engineered disulfide bonds restore chaperone-like function of DJ-1 mutants linked to familial Parkinson's disease. Biochemistry 49:5624-33
Tong, Youren; Shen, Jie (2009) alpha-synuclein and LRRK2: partners in crime. Neuron 64:771-3
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
Rappley, Irit; Gitler, Aaron D; Selvy, Paige E et al. (2009) Evidence that alpha-synuclein does not inhibit phospholipase D. Biochemistry 48:1077-83
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

Showing the most recent 10 out of 41 publications