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Article Dans Une Revue Disease Models & Mechanisms Année : 2015

Untangling dopamine-adenosine receptor-receptor assembly in experimental parkinsonism in rats

V. Fernandez-Duenas
  • Fonction : Auteur
J. J. Taura
  • Fonction : Auteur
M. Gomez-Soler
  • Fonction : Auteur
M. Lopez-Cano
  • Fonction : Auteur
C. Ledent
M. Watanabe
  • Fonction : Auteur
E. Trinquet
  • Fonction : Auteur
Jean-Philippe Pin
R. Lujan
  • Fonction : Auteur
Thierry Durroux
F. Ciruela
  • Fonction : Auteur

Résumé

Parkinson's disease (PD) is a dopaminergic-related pathology in which functioning of the basal ganglia is altered. It has been postulated that a direct receptor-receptor interaction - i.e. of dopamine D2 receptor (D2R) with adenosine A2A receptor (A2AR) (forming D2R-A2AR oligomers) - finely regulates this brain area. Accordingly, elucidating whether the pathology prompts changes to these complexes could provide valuable information for the design of new PD therapies. Here, we first resolved a long-standing question concerning whether D2R-A2AR assembly occurs in native tissue: 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 alteration of native D2R-A2AR oligomers in experimental parkinsonism, thus conferring the rationale for appropriate oligomer-based PD treatments.
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hal-01950131 , version 1 (03-06-2021)

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V. Fernandez-Duenas, J. J. Taura, Martin Cottet, M. Gomez-Soler, M. Lopez-Cano, et al.. Untangling dopamine-adenosine receptor-receptor assembly in experimental parkinsonism in rats. Disease Models & Mechanisms, 2015, 8 (1), pp.57--63. ⟨10.1242/dmm.018143⟩. ⟨hal-01950131⟩
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