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α-Synuclein overexpression increases dopamine toxicity in BE(2)-M17 cells

Marco Bisaglia1, Elisa Greggio24, Dragan Maric3, David W Miller2, Mark R Cookson2 and Luigi Bubacco1*

Author Affiliations

1 Department of Biology, University of Padova, 35121 Padova, Italy

2 Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institutes of Health, 20892 Bethesda, MD, USA

3 Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 20892 Bethesda, MD, USA

4 Current address: Department of Biology, University of Padova, Padova, Italy

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BMC Neuroscience 2010, 11:41  doi:10.1186/1471-2202-11-41

Published: 25 March 2010



Oxidative stress has been proposed to be involved in the pathogenesis of Parkinson's disease (PD). A plausible source of oxidative stress in nigral dopaminergic neurons is the redox reactions that specifically involve dopamine and produce various toxic molecules, i.e., free radicals and quinone species. α-Synuclein, a protein found in Lewy bodies characteristic of PD, is also thought to be involved in the pathogenesis of PD and point mutations and multiplications in the gene coding for α-synuclein have been found in familial forms of PD.


We used dopaminergic human neuroblastoma BE(2)-M17 cell lines stably transfected with WT or A30P mutant α-synuclein to characterize the effect of α-synuclein on dopamine toxicity. Cellular toxicity was analyzed by lactate dehydrogenase assay and by fluorescence-activated cell sorter analysis. Increased expression of either wild-type or mutant α-synuclein enhances the cellular toxicity induced by the accumulation of intracellular dopamine or DOPA.


Our results suggest that an interplay between dopamine and α-synuclein can cause cell death in a neuron-like background. The data presented here are compatible with several models of cytotoxicity, including the formation of α-synuclein oligomers and impairment of the lysosomal degradation.