dc.contributor.author | Outeiro, Tiago F. | |
dc.contributor.author | Klucken, Jochen | |
dc.contributor.author | Bercury, Kathryn | |
dc.contributor.author | Tetzlaff, Julie | |
dc.contributor.author | Putcha, Preeti | |
dc.contributor.author | Oliveira, Luis M. A. | |
dc.contributor.author | Quintas, Alexandre | |
dc.contributor.author | McLean, Pamela June | |
dc.contributor.author | Hyman, Bradley Theodore | |
dc.date.accessioned | 2011-05-05T16:08:46Z | |
dc.date.issued | 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.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:4882759 | |
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 | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731858/pdf/ | 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 |
dash.depositing.author | McLean, Pamela June | |
dc.date.available | 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 |
dc.identifier.doi | 10.1371/journal.pone.0006906 | * |
dash.contributor.affiliated | McLean, Pamela June | |
dash.contributor.affiliated | Hyman, Bradley | |