The goal of this program is to investigate the roles of conventional and 'unconventional'mitochondrial proteins in the pathogenesis of Parkinson's disease (PD). The major roles of the Molecular Core are to (i) provide the genes or gene products that are required in the individual projects, and (2) alter the expression of proteins by either knockdown (shRNA) or overexpression of their genes to facilitate the investigation of the pathogenesis of PD proposed in the individual projects. Services provided by the Molecular Core include: cDNA cloning, design and production of constructs for gene overexpression or gene silencing, assistance with generation of transient and stable transfections, production of viral vectors for in vivo gene transfer, and generation of fusion proteins containing protein transduction domain (TAT) for efficient protein transduction in in vitro and in vivo. These services will be critical for successful completion of each of the individual projects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
1P01NS059806-01A2
Application #
7760281
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
2009-07-15
Budget End
2010-06-30
Support Year
1
Fiscal Year
2009
Total Cost
$168,735
Indirect Cost
Name
University of Pittsburgh
Department
Type
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Verma, Manish; Callio, Jason; Otero, P Anthony et al. (2017) Mitochondrial Calcium Dysregulation Contributes to Dendrite Degeneration Mediated by PD/LBD-Associated LRRK2 Mutants. J Neurosci 37:11151-11165
Tapias, Victor; Hu, Xiaoping; Luk, Kelvin C et al. (2017) Synthetic alpha-synuclein fibrils cause mitochondrial impairment and selective dopamine neurodegeneration in part via iNOS-mediated nitric oxide production. Cell Mol Life Sci 74:2851-2874
Di Maio, Roberto; Barrett, Paul J; Hoffman, Eric K et al. (2016) ?-Synuclein binds to TOM20 and inhibits mitochondrial protein import in Parkinson's disease. Sci Transl Med 8:342ra78
Van Laar, Victor S; Berman, Sarah B; Hastings, Teresa G (2016) Mic60/mitofilin overexpression alters mitochondrial dynamics and attenuates vulnerability of dopaminergic cells to dopamine and rotenone. Neurobiol Dis 91:247-61
Hu, Xiaoming; Leak, Rehana K; Shi, Yejie et al. (2015) Microglial and macrophage polarization—new prospects for brain repair. Nat Rev Neurol 11:56-64
Greenamyre, J Timothy; Sanders, Laurie H; Gasser, Thomas (2015) Fruit flies, bile acids, and Parkinson disease: a mitochondrial connection? Neurology 85:838-9
Zharikov, Alevtina D; Cannon, Jason R; Tapias, Victor et al. (2015) shRNA targeting ?-synuclein prevents neurodegeneration in a Parkinson's disease model. J Clin Invest 125:2721-35
Lee, Jang-Won; Tapias, Victor; Di Maio, Roberto et al. (2015) Behavioral, neurochemical, and pathologic alterations in bacterial artificial chromosome transgenic G2019S leucine-rich repeated kinase 2 rats. Neurobiol Aging 36:505-18
Verma, Manish; Steer, Erin K; Chu, Charleen T (2014) ERKed by LRRK2: a cell biological perspective on hereditary and sporadic Parkinson's disease. Biochim Biophys Acta 1842:1273-81
Mohammadyani, Dariush; Tyurin, Vladimir A; O'Brien, Matthew et al. (2014) Molecular speciation and dynamics of oxidized triacylglycerols in lipid droplets: Mass spectrometry and coarse-grained simulations. Free Radic Biol Med 76:53-60

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