Glutamate Receptors and PD ?

Metabotropic Glutamate Receptors (mGluRs) have been shown to be involved in PD and are projected as important therapeutic targets with a neuroprotective approach for this aging disorder. The major focus for this class of GPCRs in its role in PD is through the non-cannonical non-dopaminergic pathway. Loss of Dopaminergic neurons in PD results in significant changes in other neurotransmitter systems (Glutamate and GABA) that play key roles in mediating mediating normal basal ganglia functions.

In a MPTP model of monkey, it has been demonstrated that antagonist MTEP (antagonist to mGluR5) shows anti-parkisonian effect and offers some degree of neuroprotection. This antagonist molecule is known to cross the blood-brain barrier and offer neuroprotection and this drug is cleared or flushed out very quickly. However, it is not clear what is the molecular mechanism of this mode of action. And the other question that crosses my mind is that how does this MTEP molecule really functions ? does it couple to the GPCR and induce the heterotrimeric G-protein signaling ? These are open questions and need to be explored more to figure out the mechanistic pathway.