Dopamine-Induced Conformational Changes in Alpha-Synuclein

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Dopamine-Induced Conformational Changes in Alpha-Synuclein

Show simple item record Outeiro, Tiago F. Klucken, Jochen Bercury, Kathryn Tetzlaff, Julie Putcha, Preeti Oliveira, Luis M. A. Quintas, Alexandre McLean, Pamela June Hyman, Bradley Theodore 2011-05-05T16:08:46Z 2009
dc.identifier.citation Outeiro, Tiago F., Jochen Klucken, Kathryn Bercury, Julie Tetzlaff, Preeti Putcha, Luis M. A. Oliveira, Alexandre Quintas, Pamela J. McLean, and Bradley T. Hyman. 2009. Dopamine-Induced conformational changes in alpha-synuclein. PLoS ONE 4(9): e6906. en_US
dc.identifier.issn 1932-6203 en_US
dc.description.abstract Background: Oligomerization and aggregation of α-synuclein molecules play a major role in neuronal dysfunction and loss in Parkinson's disease [1]. However, α-synuclein oligomerization and aggregation have mostly been detected indirectly in cells using detergent extraction methods [2], [3], [4]. A number of in vitro studies showed that dopamine can modulate the aggregation of α-synuclein by inhibiting the formation of or by disaggregating amyloid fibrils [5], [6], [7]. Methodology/Principal Findings: Here, we show that α-synuclein adopts a variety of conformations in primary neuronal cultures using fluorescence lifetime imaging microscopy (FLIM). Importantly, we found that dopamine, but not dopamine agonists, induced conformational changes in α-synuclein which could be prevented by blocking dopamine transport into the cell. Dopamine also induced conformational changes in α-synuclein expressed in neuronal cell lines, and these changes were also associated with alterations in oligomeric/aggregated species. Conclusion/Significance: Our results show, for the first time, a direct effect of dopamine on the conformation of α-synuclein in neurons, which may help explain the increased vulnerability of dopaminergic neurons in Parkinson's disease. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0006906 en_US
dc.relation.hasversion en_US
dash.license LAA
dc.subject molecular biology en_US
dc.subject cell biology en_US
dc.subject neuronal and glial cell biology en_US
dc.subject neuroscience en_US
dc.subject neurobiology of disease and regeneration en_US
dc.subject neurological disorders en_US
dc.subject movement disorders en_US
dc.title Dopamine-Induced Conformational Changes in Alpha-Synuclein en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US McLean, Pamela June 2011-05-05T16:08:46Z
dash.affiliation.other HMS^Neurology-Massachusetts General Hospital en_US
dash.affiliation.other HMS^Neurology-Massachusetts General Hospital en_US

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