NT-mINT:Structure-based identification of neurotrophines and pro- neurotrophines molecular interactors to target neurodegeneration and pain

The neurotrophin Nerve Growth Factor (NGF) is involved in neuronal populations’ maintenance; it has a role in the immune and endocrine systems and in the pain-signalling pathway. Alterations in NGF maturation contribute to neurodegeneration. The pharmacological potential is very high: NGF receptor agonists are of interest in neurodegeneration, whereas NGF antagonists represent novel targets for chronic pain. Few papers explored the role of small biomolecules as NGF modulators, but no molecular details are available. The project revolves around the expertise of the Institute of Crystallography of CNR and of the Laboratory for Molecular Structural Dynamics at National Institute of Chemistry (Slovenia) to elucidate the molecular features of NGF/small molecules interactions. This project will exploit solution NMR studies complemented by infrared spectroscopy, advanced structure-based approaches (molecular docking and molecular dynamics), kinetics and thermodynamics of the interactions and cell biology for a functional readout. These data will pave the way for identification of new pharmacological hits. This multidisciplinary approach is largely unexplored in the neurotrophins’ field.