MolBoolean staining reveals high proportion of D2 receptors forming A2A-D2 heteromers in striatal neurons of MPTP-lesioned parkinsonian primates

Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra pars compacta, leading to striatal dopamine deficiency. The A2A and D2 receptors form heteromeric complexes in striatal neurons that play an important modulatory role in fine-tuning motor control.The aim of this study was to assess, for the first time, the proportion of individual A2AR, of individual D2R and of A2AR-D2R heteromers (A2A-D2Het) present in a primate 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) PD model, with and without showing dyskinesias. This has been possible to achieve thanks to “MolBoolean” technique. MolBoolean is a novel immunoassay technology developed to quantify the relative proportions of monomers and dimers for a given pair of interacting proteins within cells and tissues.Analyzing and comparing the levels of free A2A and D2 receptors, as well as A2AR-D2R heterocomplexes, in striatal neurons of this non-human primate model which closely resembles Parkinson's disease pathology in humans, provides critical insights into molecular alterations relevant to the pathogenesis and treatment of Parkinson's disease.