Dopamine-Induced Conformational Changes in Alpha-Synuclein

DSpace/Manakin Repository

Dopamine-Induced Conformational Changes in Alpha-Synuclein

Show simple item record

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

Files in this item

Files Size Format View
2731858.pdf 706.8Kb PDF View/Open

This item appears in the following Collection(s)

Show simple item record

 
 

Search DASH


Advanced Search
 
 

Submitters