Dataset Information
Alpha-synuclein overexpression increases dopamine toxicity in BE2-M17 cells.
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ABSTRACT: Background
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. alpha-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 alpha-synuclein have been found in familial forms of PD.Results
We used dopaminergic human neuroblastoma BE(2)-M17 cell lines stably transfected with WT or A30P mutant alpha-synuclein to characterize the effect of alpha-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 alpha-synuclein enhances the cellular toxicity induced by the accumulation of intracellular dopamine or DOPA.Conclusions
Our results suggest that an interplay between dopamine and alpha-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 alpha-synuclein oligomers and impairment of the lysosomal degradation.
SUBMITTER: Bisaglia M
PROVIDER: S-EPMC2851596 | biostudies-literature | 2010 Mar
REPOSITORIES: biostudies-literature
Publications
Alpha-synuclein overexpression increases dopamine toxicity in BE2-M17 cells.
BMC neuroscience 20100325
<h4>Background</h4>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. alpha-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 ge ...[more]