Our work on a-synuclein is currently focussed on applying large scale screening approaches to understand the pathobiology associated with this protein, which is now known to not only be a marker of disease but also plays an active role in disease progression. In ongoing work, we have been probing the mechanism by which a-synuclein is taken up from one cell to another, a process that has been proposed to be important in the spread of disease between brain regions. Using fluorescently labelled recombinant forms of a-synuclein we have initiated screens against uptake of the protein. Candidate modifiers are currently being validated to see if any are informative for mechanism of uptake, but initial results suggest that they are in a common pathway related to intracellular vesicular trafficking.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000939-09
Application #
9351987
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Aging
Department
Type
DUNS #
City
State
Country
Zip Code
Bandres-Ciga, Sara; Cookson, Mark R (2017) Alpha-synuclein triggers T-cell response. Is Parkinson's disease an autoimmune disorder? Mov Disord 32:1327
Wang, Wei; Nguyen, Linh T T; Burlak, Christopher et al. (2016) Caspase-1 causes truncation and aggregation of the Parkinson's disease-associated protein ?-synuclein. Proc Natl Acad Sci U S A 113:9587-92
Kumaran, Ravindran; Cookson, Mark R (2015) Pathways to Parkinsonism Redux: convergent pathobiological mechanisms in genetics of Parkinson's disease. Hum Mol Genet :
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Wang, Wei; Perovic, Iva; Chittuluru, Johnathan et al. (2011) A soluble ?-synuclein construct forms a dynamic tetramer. Proc Natl Acad Sci U S A 108:17797-802
Bisaglia, Marco; Greggio, Elisa; Maric, Dragan et al. (2010) Alpha-synuclein overexpression increases dopamine toxicity in BE2-M17 cells. BMC Neurosci 11:41
Cookson, Mark R (2009) alpha-Synuclein and neuronal cell death. Mol Neurodegener 4:9

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