par Fernández-Dueñas, Víctor;Taura, Jaume J.J.;Gómez-Soler, Maricel;López-Cano, Marc;Ciruela, Francisco;Cottet, Martin;Pin, Jean-Philippe;Durroux, Thierry;Ledent, Catherine
;Watanabe, Masahiko;Trinquet, Eric;Luján, Rafael
Référence Disease Models and Mechanisms, 8, 1, page (57-63)
Publication Publié, 2015-01

Référence Disease Models and Mechanisms, 8, 1, page (57-63)
Publication Publié, 2015-01
Article révisé par les pairs
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 oligomerbased PD treatments. |