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Research Article
Untangling dopamine-adenosine receptor assembly in experimental parkinsonism
Víctor Fernández-Dueñas, Jaume J. Taura, Martin Cottet, Maricel Gómez-Soler, Marc López-Cano, Catherine Ledent, Masahiko Watanabe, Eric Trinquet, Jean-Philippe Pin, Rafael Luján, Thierry Durroux, Francisco Ciruela
Disease Models & Mechanisms 2014 : dmm.018143 doi: 10.1242/dmm.018143 Published 14 November 2014
Víctor Fernández-Dueñas
Universitat de Barcelona, Barcelona, Spain;
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Jaume J. Taura
Universitat de Barcelona, Barcelona, Spain;
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Martin Cottet
INSERM-CNRS, Montpellier, France;
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Maricel Gómez-Soler
Universitat de Barcelona, Barcelona, Spain;
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Marc López-Cano
Universitat de Barcelona, Barcelona, Spain;
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Catherine Ledent
Université Libre de Bruxelles, Brussels, Belgium;
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Masahiko Watanabe
Hokkaido University School of Medicine, Sapporo, Japan;
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Eric Trinquet
Cisbio Bioessays, Codolet, France;
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Jean-Philippe Pin
INSERM-CNRS, Montpellier, France;
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Rafael Luján
UCLM, Albacete, Spain
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Thierry Durroux
INSERM-CNRS, Montpellier, France;
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Francisco Ciruela
Universitat de Barcelona, Barcelona, Spain;
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Abstract

Parkinson’s disease (PD) is a dopaminergic-related pathology in which basal ganglia functioning are altered. It has been postulated that a direct receptor-receptor – i.e. dopamine D2 receptor (D2R) and adenosine A2A receptor (A2AR) – interaction may be finely regulating this brain area. Accordingly, elucidating whether the pathology prompts changes on these structures could grant valuable information for the design of new PD therapies. Here, we first resolved a long-standing question concerning D2R-A2AR assembly in native tissue. Thus, by means of different complementary experimental approaches (i.e. immunoelectron microscopy, proximity ligation assay and TR-FRET), we unambiguously identified native D2R/A2AR oligomers in rat striatum. Subsequently, we determined that under pathological conditions (i.e. in a rat PD model) D2R-A2AR interaction was impaired. Collectively, these results provide definitive evidence for a native D2R/A2AR oligomer alteration in experimental parkinsonism, thus conferring the rationale for appropriate oligomer-based PD treatments.

  • Received September 4, 2014.
  • Accepted November 10, 2014.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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Untangling dopamine-adenosine receptor assembly in experimental parkinsonism
Víctor Fernández-Dueñas, Jaume J. Taura, Martin Cottet, Maricel Gómez-Soler, Marc López-Cano, Catherine Ledent, Masahiko Watanabe, Eric Trinquet, Jean-Philippe Pin, Rafael Luján, Thierry Durroux, Francisco Ciruela
Disease Models & Mechanisms 2014 : dmm.018143 doi: 10.1242/dmm.018143 Published 14 November 2014
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Untangling dopamine-adenosine receptor assembly in experimental parkinsonism
Víctor Fernández-Dueñas, Jaume J. Taura, Martin Cottet, Maricel Gómez-Soler, Marc López-Cano, Catherine Ledent, Masahiko Watanabe, Eric Trinquet, Jean-Philippe Pin, Rafael Luján, Thierry Durroux, Francisco Ciruela
Disease Models & Mechanisms 2014 : dmm.018143 doi: 10.1242/dmm.018143 Published 14 November 2014

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