Dopamine-induced conformational changes in alpha-synuclein.
Oligomerization and aggregation of alpha-synuclein molecules play a major role in neuronal dysfunction and loss in Parkinson's disease [1]. However, alpha-synuclein oligomerization and aggregation have mostly been detected indirectly in cells using detergent extraction methods [2], [3], [4]. A...
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doaj-83ed2a47e6c6447f8709de53d5c6309f2020-11-24T22:04:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-09-0149e690610.1371/journal.pone.0006906Dopamine-induced conformational changes in alpha-synuclein.Tiago F OuteiroJochen KluckenKathryn BercuryJulie TetzlaffPreeti PutchaLuis M A OliveiraAlexandre QuintasPamela J McLeanBradley T HymanOligomerization and aggregation of alpha-synuclein molecules play a major role in neuronal dysfunction and loss in Parkinson's disease [1]. However, alpha-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 alpha-synuclein by inhibiting the formation of or by disaggregating amyloid fibrils [5], [6], [7].Here, we show that alpha-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 alpha-synuclein which could be prevented by blocking dopamine transport into the cell. Dopamine also induced conformational changes in alpha-synuclein expressed in neuronal cell lines, and these changes were also associated with alterations in oligomeric/aggregated species.Our results show, for the first time, a direct effect of dopamine on the conformation of alpha-synuclein in neurons, which may help explain the increased vulnerability of dopaminergic neurons in Parkinson's disease.http://europepmc.org/articles/PMC2731858?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tiago F Outeiro Jochen Klucken Kathryn Bercury Julie Tetzlaff Preeti Putcha Luis M A Oliveira Alexandre Quintas Pamela J McLean Bradley T Hyman |
spellingShingle |
Tiago F Outeiro Jochen Klucken Kathryn Bercury Julie Tetzlaff Preeti Putcha Luis M A Oliveira Alexandre Quintas Pamela J McLean Bradley T Hyman Dopamine-induced conformational changes in alpha-synuclein. PLoS ONE |
author_facet |
Tiago F Outeiro Jochen Klucken Kathryn Bercury Julie Tetzlaff Preeti Putcha Luis M A Oliveira Alexandre Quintas Pamela J McLean Bradley T Hyman |
author_sort |
Tiago F Outeiro |
title |
Dopamine-induced conformational changes in alpha-synuclein. |
title_short |
Dopamine-induced conformational changes in alpha-synuclein. |
title_full |
Dopamine-induced conformational changes in alpha-synuclein. |
title_fullStr |
Dopamine-induced conformational changes in alpha-synuclein. |
title_full_unstemmed |
Dopamine-induced conformational changes in alpha-synuclein. |
title_sort |
dopamine-induced conformational changes in alpha-synuclein. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2009-09-01 |
description |
Oligomerization and aggregation of alpha-synuclein molecules play a major role in neuronal dysfunction and loss in Parkinson's disease [1]. However, alpha-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 alpha-synuclein by inhibiting the formation of or by disaggregating amyloid fibrils [5], [6], [7].Here, we show that alpha-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 alpha-synuclein which could be prevented by blocking dopamine transport into the cell. Dopamine also induced conformational changes in alpha-synuclein expressed in neuronal cell lines, and these changes were also associated with alterations in oligomeric/aggregated species.Our results show, for the first time, a direct effect of dopamine on the conformation of alpha-synuclein in neurons, which may help explain the increased vulnerability of dopaminergic neurons in Parkinson's disease. |
url |
http://europepmc.org/articles/PMC2731858?pdf=render |
work_keys_str_mv |
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