Dopamine-Induced Conformational Changes in Alpha-Synuclein

DSpace/Manakin Repository

Dopamine-Induced Conformational Changes in Alpha-Synuclein

Citable link to this page

. . . . . .

Title: Dopamine-Induced Conformational Changes in Alpha-Synuclein
Author: Outeiro, Tiago F.; Klucken, Jochen; Bercury, Kathryn; Tetzlaff, Julie; Putcha, Preeti; Oliveira, Luis M. A.; Quintas, Alexandre; McLean, Pamela June; Hyman, Bradley Theodore

Note: Order does not necessarily reflect citation order of authors.

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.
Full Text & Related Files:
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.
Published Version: doi:10.1371/journal.pone.0006906
Other Sources:
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at
Citable link to this page:

Show full Dublin Core record

This item appears in the following Collection(s)


Search DASH

Advanced Search