Untangling dopamine-adenosine receptor assembly in experimental parkinsonism

• Published in: Disease models & mechanisms
• Main Authors: Fernández-Dueñas, Víctor, Taura, Jaume J., Cottet, Martin, Gómez-Soler, Maricel, López-Cano, Marc, Ledent, Catherine, Watanabe, Masahiko, Trinquet, Eric, Pin, Jean-Philippe, Luján, Rafael, Durroux, Thierry, Ciruela, Francisco
• Format: Journal Article
• Language: English
• Published: 01.01.2014
• ISSN: 1754-8403; 1754-8411
• DOI: 10.1242/dmm.018143

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.