Figure 1.

Schematic presentation of mGluRs cell signalling pathways. Likely, other GPCRs and mGluRs are located at the cell membrane that binds to extracellular substances and transmits signals to intracellular molecules called G-protein (G-α, -β, and -γ) Upon agonist activation, both group II and III mGluRs are coupled predominantly to Gi/o proteins, which mediate the downstream inhibition of adenylyl cyclase activity via Gα_i/o, decreasing the levels of cAMP. Gβγ subunits modulate voltage-dependent ion channels, inhibiting Ca²⁺ and limiting presynaptic glutamate or GABA release. Group II and III mGluRs also activate PI3K/Akt and MAPK pathways and enhance neuroprotection by increasing the production of neurotrophic factors [58]. In the post-synapse, following glutamate binding, group I mGluRs uncouple Gα_q/11 proteins, stimulate PLCβ1, and activate DAG and IP3, which increase intracellular Ca²⁺ efflux. Both Ca²⁺ and DAG activate PKC, which has been proposed to activate MEK/ERK1/2 signalling. Furthermore, mGluR1/5 interacts with Homer proteins, which activate Shank proteins. This complex of Homer proteins and group I mGluRs activates Akt through a mechanism that involves PI3K, PDK1, and PIKE, promoting neuroprotection [8]. Physical interaction between elements is represented by a continuous line.