The Chemical Neurosciences thematic develops an integrated chemical biology approach to decipher and modulate synaptic mechanisms at the molecular level. It combines rational ligand design, molecular modeling and protein-protein interaction analysis with advanced fluorescence imaging to target key synaptic proteins.

Major achievements include the first drug-like ligands of vesicular glutamate transporters (VGLUTs), enabling selective modulation of glutamatergic transmission from biochemistry to in vivo behavior. We also highlight that flexible and dynamic protein-protein interfaces, such as dopamine-NMDA receptor heteromers, can be pharmacologically targeted, overturning the concept of “undruggable” synaptic complexes.

Together, these results provide innovative molecular tools and therapeutic perspectives for neurological and psychiatric disorders.