Outeiro, Tiago F.Klucken, JochenBercury, KathrynTetzlaff, JuliePutcha, PreetiOliveira, Luis M. A.Quintas, AlexandreMcLean, Pamela JuneHyman, Bradley2011-05-052009Outeiro, 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): e6906.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:4882759Background: 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-USmolecular biologycell biologyneuronal and glial cell biologyneuroscienceneurobiology of disease and regenerationneurological disordersmovement disordersJournal Article2011-05-0510.1371/journal.pone.0006906