To strengthen the existing knowledge on P2XRs role in neurodegeneration and depression pathophysiology, thus contributing to training a new generation of translational experts in this field and ultimately facilitating the passage of P2XR-based research to the clinics.
1) To review established and develop novel protocols for the in vivo administration of P2XR agonists and antagonists in selected neurodegenerative diseases and mood disorders (e.g., depression).
2) To promote the interaction between PRESTO and industrial and academic members to accelerate development testing of blood-brain barrier permeant P2XR-targeting drugs.
Task 2.1: Collect and analyze recent data from patient cohorts and preclinical models of depression, bipolar disorder, multiple sclerosis, epilepsy, Alzheimer’s disease, neuropathic pain. This aim will be accomplished by presenting and discussing data from PRESTO members and external experts in two dedicated conferences.
Task 2.2: Write consensus protocols to guide PRESTO members and other investigators in selecting the most appropriate P2XR-targeting drugs and most effective administration routes for preclinical experiments in models of neurodegenerative diseases. This will warrant data reproducibility and accelerate the transfer to the clinics. These consensus protocols will be published in major journals in the field (consensus papers).
Task 2.3: Establish collaboration for joint experimental projects to test the efficacy of novel CNS-acting, P2XR-targeting drugs developed by the Action members and/or the members from Industries.
Task 2.4: Organize Short-Term Scientific Missions for both young and established investigators at academic and industrial facilities to learn novel techniques and experimental systems to investigate neurodegenerative diseases, with particular emphasis on the replacement of in vivo models with in vitro systems.
Task 2.5: Organize a training school in advanced fluorescence and bio-luminescence techniques (single- cell intracellular Ca2+ analysis, mitochondrial structure, and function, P2XR signalosome FRET investigation, intra- and eATP measurement by engineered luciferase probes) to investigate signal transduction in in vitro cell culture and organotypic systems and in animal models of neurodegenerative diseases.