Impacting Neuronal and Vascular Cellular Signal Transduction through the Metabotropic Glutamate Receptor System

The metabotropic glutamate receptor (mGluR) system plays a critical role to foster the proper development of an organism. Yet, what has unfolded over the last decade is the vital interplay between the mGluR system and the fate of a cell during both acute and chronic neurodegenerative disorders. Through the coupling to guanosine-nucleotide-binding proteins, the mGluR system drives a series of cellular pathways that impact upon the apoptotic induction of genomic DNA fragmentation, membrane phosphatidylserine (PS) residue exposure, and the inflammatory activation of microglia in the brain. A broad array of cellular pathways appear to be governed by the mGluR system and include the protein kinases PKA, PKB, and PKC. In addition, distinct modulation of mitochondrial membrane potential, caspase activity, intracellular pH, and endonucleases are required to ultimately preserve the integrity of a cell. Cytoprotection by the mGluR system is clinically significant, since neuronal and vascular cell populations can benefit from immediate and delayed protection by mGluRs. Although mGluR activity may not always promote the survival of a cell and final outcome can be intimately linked to the environmental stimulus, future work with the mGluR system will guide the development of novel strategies to prevent cellular injury by this glutamate receptor family.