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. |