Topic: mGlu2

Monoclonal antibodies are commonly used as a treatment for a variety of diseases, but very few are used to treat neurological conditions. One reason is that their delivery into the brain is hampered by the blood-brain barrier. Small antibody fragment from camelids, called Nanobody®, are good alternative to these conventional antibodies. In the present work, we study how brain-penetrating nanobodies reach the brain after peripheral administration in mice by developping different approaches. We used nanobodies specific to a metabotropic glutamate (mGlu) receptor, the mGlu2 subtype, as a model. F

The eight metabotropic glutamate (mGlu1-8) receptors are key players in the modulation of the synaptic transmission. They have long been considered as homodimeric entities since they function only as mandatory dimers. However, it has been recently proposed that they can also heterodimerize in specific combinations, adding 16 new dimeric mGlu entities. This implied to characterize each heterodimer to develop tools to detect specifically their expression and activity in native tissues.The mGlu7 homodimers have a very low affinity for glutamate (mM) compared to that of the other mGlus (µM). It wa

Metabotropic glutamate receptor 2 (mGlu2) is a G protein-coupled receptor expressed in the central nervous system and canonically coupled to Gi/o protein. mGlu2 receptor is the main target of a new generation of antipsychotics which showed unprecedent efficiency on negative and cognitive symptoms of Schizophrenia, which were so far resisting to actual antipsychotics. However, the molecular mechanisms regulating the antipsychotic properties of mGlu2 receptor stimulation remain unclear. In a recent interactomic screen (Philibert et al., Science Advances, 2024), we demonstrated that endogenous mG

The dentate gyrus (DG) of the ventral hippocampus is a key hub critical for the responses to prolonged chronic stress and antidepressant drugs, including the antidepressant candidate acetyl-L-carnitine (LAC). Prior studies from our and other laboratories showed transcriptome-wide signatures in this brain area with robust changes in genes important for neuronal plasticity, including the metabotropic glutamate receptor-2 (mGlu2), and insulin signaling pathways after chronic stress, and that these changes are ameliorated by short-term administration of LAC. Here, we used 10X Genomics droplet-base

Metabotropic glutamate receptor 2 (mGlu2) attracts particular attention as a possible target for a new class of antipsychotics. However, the signaling pathways transducing the effects of mGlu2 in the brain remain poorly characterized. In a recent article published in Sciences Advances (doi/10.1126/sciadv.adg1679), we addressed this issue by identifying native mGlu2 interactome in mouse prefrontal cortex. Nanobody-based affinity purification and mass spectrometry identified 149 candidate mGlu2 partners, including the neurotrophin receptor TrkB. The later interaction was confirmed both in cultur