Nanobodies against the glutamatergic synapse: new drugs and tools?

GPCR seminar
Speaker: Dr Philippe Rondard, IGF, France

Abstract: In the glutamatergic synapses, the different metabotropic glutamate receptors (mGluRs) modulate neurotransmission and are interesting therapeutic targets for the treatment of many neurological and psychiatric diseases. Developing mGluR subtype-specific modulators is challenging since the glutamate binding pocket is conserved, and the allosteric modulators have the inconvenient to be hydrophobic. We recently took advantage of the original structure of the mGluRs to develop new ligands such as camelid single chain antibodies, or nanobodies. We describe the characterization of high affinity nanobodies that activate the receptor mGlu2 both in vitro and in vivo. Our results show that nanobodies could be used both in vitro and in vivo as new pharmacological agents to modulate the activity of mGluRs and as tools to investigate the native mGluRs.

Everybody is welcome!