PROJECT: JTC2008: heteropark

General aim: Translational research looking for a novel therapy for Parkinson?s disease based on targeting G protein-coupled receptor hetero/oligomers. 1: Target selection: Identifying receptor heteromers as targets for Parkinson?s disease in animal models. Looking for qualitative and/or quantitative changes on receptor heteromer expression retrograde to dopaminergic depletion. Preliminary results performed in the rat model of PD indicate that there are qualitative and quantitative differences in heteromerization. 2: Synthesis of tailored drugs acting on pre-selected targets/heteromers. 3: Target validation. Evaluation of safety and efficacy of newly-designed drugs for the alleviation of motor symptoms and dyskinesias in animal models of PD. MILESTONES: M1. Heteromer expression retrograde to dopaminergic depletion in rat and primate models of PD. Preliminary results performed in the rat model of PD indicate that there are qualitative and quantitative differences in heteromerization. M2. Synthesis of newly-designed drugs targeting either individual receptors within heteromers, having a dual behaviour (acting on two receptors) or selectively targeting receptor heteromers. M3. Selection of compounds or combinations of compounds simultaneously affording the highest symptomatic relief without safety concerns.