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. We have been able to validate one potential receptor that is required for the transmission of proteins in cells and in vivo and are currently working on the underlying mechanisms. We are also working on ways to damage neurons in vivo using a-synuclein, either expressed from viral vectors or by addition of preformed fibrils. As part of this work, we have developed midbrain 'organoids' from human cells. Ongoing work is trying to cross validate results across these platforms.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000939-12
Application #
10005771
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
2019
Total Cost
Indirect Cost
Name
National Institute on 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 :
Cookson, Mark R (2014) Lardy brains make Parkinson's disease mice worse. J Neurochem 131:697-8
Dehay, Benjamin; Martinez-Vicente, Marta; Caldwell, Guy A et al. (2013) Lysosomal impairment in Parkinson's disease. Mov Disord 28:725-32
Choi, Jae Hyuk; Stubblefield, Barbara; Cookson, Mark R et al. (2011) Aggregation of ?-synuclein in brain samples from subjects with glucocerebrosidase mutations. Mol Genet Metab 104:185-8
Cookson, Mark R (2011) A feedforward loop links Gaucher and Parkinson's diseases? Cell 146:9-11
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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