Abstract

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. We have been working on high content imaging approaches to follow synuclein uptake and toxicity in cells in culture. We have been able to show that a variety of cell types can uptake preformed fibrils that are labelled with fluorophores to allow for simple assays of internalization. The ongoing objective of the work is to port this assay into a multi well format so we can then screen siRNA libraries for genes that modify uptake.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000939-07
Application #
8931626
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2014
Total Cost
Indirect Cost

  Institution

Name
Aging
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

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
Liu, Zhihua; Meray, Robin K; Grammatopoulos, Tom N et al. (2009) Membrane-associated farnesylated UCH-L1 promotes alpha-synuclein neurotoxicity and is a therapeutic target for Parkinson's disease. Proc Natl Acad Sci U S A 106:4635-40

Showing the most recent 10 out of 13 publications