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Publication : Untangling dopamine-adenosine receptor-receptor assembly in experimental parkinsonism in rats.

First Author  Fernández-Dueñas V Year  2015
Journal  Dis Model Mech Volume  8
Issue  1 Pages  57-63
PubMed ID  25398851 Mgi Jnum  J:217393
Mgi Id  MGI:5613840 Doi  10.1242/dmm.018143
Citation  Fernandez-Duenas V, et al. (2015) Untangling dopamine-adenosine receptor-receptor assembly in experimental parkinsonism in rats. Dis Model Mech 8(1):57-63
abstractText  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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