Abstract

The aim of this core is to provide personnel to utilize modern techniques in gene expression arrays, protein expression analysis, and high-throughput screening to support reseaarch in projects 1-3. One individual will be primarily engaged in gene expression studies, providing a detailed comparison between tissue from patients with Lewy body-associated diseases; DLBD, PD, and MSA and transgenic animals (project 3) and cell culture models (project 2). A second individual will be utilized to convert the assays developed in conjunction with projects l and 2 into assay suitable for high-throughput screens. This individual will subsequently screen selected small-molecule libraries to find molecules that alter these processes. These molecules will be used as tools to test models pathogenesis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
5P50NS038375-03
Application #
6499890
Study Section
Special Emphasis Panel (ZNS1)
Project Start
2001-08-01
Project End
2002-07-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
3
Fiscal Year
2001
Total Cost
$248,088
Indirect Cost

  Institution

Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
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