The pathogenesis of Parkinson's Disease (PD) involves death of dopaminergic neurons in the substantia nigra and Lewy bodies in the substantia nigra and other brain regions, including brainstem monominergic neurons, and neurons in the cerebral cortex. Alpha-Synuclein mutations cause autosomal dominant forms of PD clinically indistinguishable from sporadic PD. In addition, alpha-synuclein is a component of the Lewy bodies in both PD and in Diffuse Lewy Body disease.
In Specific Aim #1 we will identify protein interactors for alpha-synuclein using the yeast two- hybrid system and confirm the interactions using biochemical techniques.
In Specific Aim #2 we will characterize the cellular pattern of expression of these interactors in comparison with alpha-synuclein.
In Specific Aim #3 we will make a cell model which reproduces some of the features of PD using transient and stable expression of alpha-synuclein and interacting proteins in cell culture. We will study the pathways of cell death which are activated in this model. Taken together these studies will shed light on the molecular and cellular pathogenesis of PD and provide models for testing of experimental therapeutics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
1P50NS038377-01
Application #
6112674
Study Section
Project Start
1998-09-30
Project End
1999-08-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Hinkle, Jared T; Perepezko, Kate; Mari, Zoltan et al. (2018) Perceived Treatment Status of Fluctuations in Parkinson Disease Impacts Suicidality. Am J Geriatr Psychiatry 26:700-710
Kaji, Seiji; Maki, Takakuni; Kinoshita, Hisanori et al. (2018) Pathological Endogenous ?-Synuclein Accumulation in Oligodendrocyte Precursor Cells Potentially Induces Inclusions in Multiple System Atrophy. Stem Cell Reports 10:356-365
Yun, Seung Pil; Kim, Donghoon; Kim, Sangjune et al. (2018) ?-Synuclein accumulation and GBA deficiency due to L444P GBA mutation contributes to MPTP-induced parkinsonism. Mol Neurodegener 13:1
Hinkle, Jared T; Perepezko, Kate; Rosenthal, Liana S et al. (2018) Markers of impaired motor and cognitive volition in Parkinson's disease: Correlates of dopamine dysregulation syndrome, impulse control disorder, and dyskinesias. Parkinsonism Relat Disord 47:50-56
Berger, Nathan A; Besson, Valerie C; Boulares, A Hamid et al. (2018) Opportunities for the repurposing of PARP inhibitors for the therapy of non-oncological diseases. Br J Pharmacol 175:192-222
Wu, Xinyan; Zahari, Muhammad Saddiq; Renuse, Santosh et al. (2018) Quantitative phosphoproteomic analysis reveals reciprocal activation of receptor tyrosine kinases between cancer epithelial cells and stromal fibroblasts. Clin Proteomics 15:21
Blauwendraat, Cornelis; Pletnikova, Olga; Geiger, Joshua T et al. (2018) Genetic analysis of neurodegenerative diseases in a pathology cohort. Neurobiol Aging :
Heo, Seok; Diering, Graham H; Na, Chan Hyun et al. (2018) Identification of long-lived synaptic proteins by proteomic analysis of synaptosome protein turnover. Proc Natl Acad Sci U S A 115:E3827-E3836
Dawson, Ted M; Golde, Todd E; Lagier-Tourenne, Clotilde (2018) Animal models of neurodegenerative diseases. Nat Neurosci 21:1370-1379
Lee, Saebom; Kim, Sangjune; Park, Yong Joo et al. (2018) The c-Abl inhibitor, Radotinib HCl, is neuroprotective in a preclinical Parkinson's disease mouse model. Hum Mol Genet 27:2344-2356

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