The overall goal of this program project is to investigate mechanisms by which alterations in mitochondrial protein function(s) contribute to neuronal degeneration related to Parkinson's disease (PD). Thus, a central Neuropathology Core to examine alterations in subcellular protein distribution, post-translational modification, and association with neuronal injury/death markers in PD/Lewy body disease (LBD) patient brain tissues and related model systems forms an essential component interfacing with each of the individual projects. The Core will be directed by a practicing neuropathologist with expertise in Lewy body diseases and subcellular protein trafficking in PD models, and draw upon extensive resources of the University of Pittsburgh Brain Bank. The neuropathology core will apply multi-label fluorescence or biochemical techniques to study protein localization, phosphorylation and macromolecular interactions in appropriately fixed or frozen tissues, in defining selection criteria to obtain pertinent regions of brain from diseased and matched control subjects, and in standardizing quantitative image analysis protocols for experimental material and human brain tissue studies across the projects. The core personnel have ongoing, productive collaborations with the individual project leaders, as reflected in shared manuscripts and preliminary data. Given the success of these interactions, we expect a continued expansion of translational efforts between disease models and human pathology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS059806-05
Application #
8505556
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
5
Fiscal Year
2013
Total Cost
$87,263
Indirect Cost
$29,663
Name
University of Pittsburgh
Department
Type
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
An, Chengrui; Shi, Yejie; Li, Peiying et al. (2014) Molecular dialogs between the ischemic brain and the peripheral immune system: dualistic roles in injury and repair. Prog Neurobiol 115:6-24
Tapias, Victor; Greenamyre, J Timothy (2014) A rapid and sensitive automated image-based approach for in vitro and in vivo characterization of cell morphology and quantification of cell number and neurite architecture. Curr Protoc Cytom 68:12.33.1-12.33.22
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
Hu, Xiaoming; Liou, Anthony K F; Leak, Rehana K et al. (2014) Neurobiology of microglial action in CNS injuries: receptor-mediated signaling mechanisms and functional roles. Prog Neurobiol 119-120:60-84
Tapias, Victor; Cannon, Jason R; Greenamyre, J Timothy (2014) Pomegranate juice exacerbates oxidative stress and nigrostriatal degeneration in Parkinson's disease. Neurobiol Aging 35:1162-76
Sanders, Laurie H; McCoy, Jennifer; Hu, Xiaoping et al. (2014) Mitochondrial DNA damage: molecular marker of vulnerable nigral neurons in Parkinson's disease. Neurobiol Dis 70:214-23
Sanders, Laurie H; Laganiere, Josee; Cooper, Oliver et al. (2014) LRRK2 mutations cause mitochondrial DNA damage in iPSC-derived neural cells from Parkinson's disease patients: reversal by gene correction. Neurobiol Dis 62:381-6
Wang, Jiayin; Shi, Yejie; Zhang, Lili et al. (2014) Omega-3 polyunsaturated fatty acids enhance cerebral angiogenesis and provide long-term protection after stroke. Neurobiol Dis 68:91-103
Tapias, Victor; Greenamyre, J Timothy; Watkins, Simon C (2013) Automated imaging system for fast quantitation of neurons, cell morphology and neurite morphometry in vivo and in vitro. Neurobiol Dis 54:158-68
Sanders, Laurie H; Greenamyre, J Timothy (2013) Oxidative damage to macromolecules in human Parkinson disease and the rotenone model. Free Radic Biol Med 62:111-20

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