Metabotropic glutamate receptors promote neuronal and vascular plasticity through novel intracellular pathways.

Abstract

During the initial development and maturation of an individual, the metabotropic glutamate receptor (mGluR) system becomes a necessary component for the critical integration of cellular function and plasticity. In addition to the maintenance of cellular physiology, the mGluR system plays a critical role during acute and chronic degenerative disorders of the central nervous system. By coupling to guanosine-nucleotide-binding proteins (G-proteins), the mGluR system employs a broad range of signal transduction systems to regulate cell survival and injury. More commonly, it is the activation of specific mGluR subtypes that can prevent programmed cell death (PCD) consisting of two distinct pathways of genomic DNA degradation and membrane phosphatidylserine (PS) residue exposure. To offer this cellular protection, mGluRs modulate a series of down-stream cellular pathways that include protein kinases, mitochondrial membrane potential, cysteine proteases, intracellular pH, endonucleases, and mitogen activated protein kinases. Prevention of cellular injury by the mGluR system is directly applicable to clinical disability, since immediate and delayed injury paradigms demonstrate the ability of this system to reverse PCD in both neuronal and vascular cell populations. Further understanding of the intricate pathways that determine the protective nature of the mGluR system will provide new therapeutic avenues for the treatment of neurodegenerative disorders.