1. Parkinson’s disease (PD) is one of the most common chronic progressive neurodegenerative diseases. PD has a prevalence of 1.2 million people in Europe and an annual cost of 11 billion Euros, being one of the 12 most costly brain diseases in Europe. What do we ask to research? A strong translational character: Understanding the brain functioning at molecular, cellular and system level is essential to unravel pathogenesis of brain diseases. How to impact on disease onset and progression, to effectively help those citizens leaving with PD Consensus document on brain research, J. Olesen, M Baker, T Freund, M Di Luca, J Mendlewicz, I Regan, M Westphal - EBC - J Neurol Neurosurg Psychiatry 2006 Research on Parkinson diseases in Europe

2. The needs Key points still need to be addressed and require intense research effort. REPLACES will handle the following issues: 1.Development of novel and appropriate chronic animal models for basic research, where to address the study of brain plasticity in corticostriatal pathways. 2.Identification of changes in low abundance proteins and characterization of their functions based on protein-protein interactions and the application of advanced proteomic methodologies. 3.Identification of therapeutic proteins as well as targets for drug intervention. In particular, the possible role of factors in the pathophysiology of PD, and their potential role in its treatment, will be further explored.

3. REPLACES will study a new aspect of pathogenesis of Parkinson Disease that is the interplay between two transmitters in the brain: dopamine and glutamate Specific objectives are: 1.Characterization of the pathological mechanisms underlying altered synaptic function in experimental animal models and in PD patients. 3. Restorative approaches for synaptic alterations in PD animal models.

4. REPLACES The study of the synaptic changes occurring in an experimental model of Parkinson Disease is of critical importance in order to develop therapeutic strategies to prevent neuronal death and to restore physiological synaptic function at corticostriatal synapses where glutamate and dopamine interplay.