The regulation of the NCS-1/Ric8a protein complex with small molecules for synapse function control
Protein Structure and Function
Instituto de Química Física "Rocasolano" CSIC (IQFR)
DESCRIPTION OF THE OFFER
The complex formed by the Ca2+ sensor neuronal calcium sensor 1 (NCS-1) and the guanine exchange factor protein Ric8a co-regulates synapse number and probability of neurotransmitter release, emerging as a potential therapeutic target for diseases affecting synapses. Recently, we have demonstrated the druggability of the NCS-1/Ric8a interface. We have shown that it is possible to inhibit this protein complex with small molecules to restores normal synapse number and associative learning in a Fragile X Syndrome animal model. Following the same idea, it is possible to speculate that the stabilization of the protein complex with small molecules would be a good therapeutic approach to increase the abnormally low synapse number found in neurodegenerative diseases such as Alzheimer or Huntington, thus contributing to the improvement of cognitive skills and memory. We intend to carry out crystallographic, computational, biochemical and biophysical studies on the NCS-1/Ric8a complex, that permit to understand protein-protein and protein-ligand interactions to finally develop new regulatory molecules with therapeutic potential in neurodegenerative diseases.
Biomolecules & Cell D.
Mª José Sánchez Barrena