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dc.contributor.authorOuteiro, Tiago F.
dc.contributor.authorKlucken, Jochen
dc.contributor.authorBercury, Kathryn
dc.contributor.authorTetzlaff, Julie
dc.contributor.authorPutcha, Preeti
dc.contributor.authorOliveira, Luis M. A.
dc.contributor.authorQuintas, Alexandre
dc.contributor.authorMcLean, Pamela June
dc.contributor.authorHyman, Bradley Theodore
dc.date.accessioned2011-05-05T16:08:46Z
dc.date.issued2009
dc.identifier.citationOuteiro, 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.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4882759
dc.description.abstractBackground: 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.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0006906en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731858/pdf/en_US
dash.licenseLAA
dc.subjectmolecular biologyen_US
dc.subjectcell biologyen_US
dc.subjectneuronal and glial cell biologyen_US
dc.subjectneuroscienceen_US
dc.subjectneurobiology of disease and regenerationen_US
dc.subjectneurological disordersen_US
dc.subjectmovement disordersen_US
dc.titleDopamine-Induced Conformational Changes in Alpha-Synucleinen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorMcLean, Pamela June
dc.date.available2011-05-05T16:08:46Z
dash.affiliation.otherHMS^Neurology-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Neurology-Massachusetts General Hospitalen_US
dc.identifier.doi10.1371/journal.pone.0006906*
dash.contributor.affiliatedMcLean, Pamela June
dash.contributor.affiliatedHyman, Bradley


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