Details

Autor(en) / Beteiligte

• Outeiro, Tiago F
• Klucken, Jochen
• Bercury, Kathryn
• Tetzlaff, Julie
• Putcha, Preeti
• Oliveira, Luis M A
• Quintas, Alexandre
• McLean, Pamela J
• Hyman, Bradley T
• Cookson, Mark R.

Titel

Dopamine-induced conformational changes in alpha-synuclein

Ist Teil von

• PloS one, 2009-09, Vol.4 (9), p.e6906-e6906

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.