Metabotropic glutamate receptors as targets for multipotential treatment of neurological disorders.
Glutamate is a major excitatory neurotransmitter in the CNS that is involved in numerous cellular functions, including cell death and survival. Metabotropic glutamate receptors (mGluR) are G-protein coupled receptors that have been classified into three groups on the basis of signal transduction pathways and pharmacological profiles. Group I, II, and III mGluRs are found on cell types within and peripheral to the CNS, including neurons, microglia, astrocytes, oligodendrocytes, T- and B-cell lymphocytes, osteoblasts, hepatocytes, and endothelial cells, among others. These receptors have a number of effects on cells that can influence outcome after trauma, including reducing neuronal and oligodendroglial cell death, inflammation, and endothelial permeability. Thus, mGluRs are a promising multipotential therapeutic approach. Because the pathology of CNS trauma and neurodegeneration is multifactorial (including, for example, oxidative stress, mitochondrial breakdown, and inflammation), therapies that serve to modulate multiple pathophysiological pathways may prove more effective than those directed at a single target. This review examines the multipotential therapeutic utility of mGluR modulation in acute and chronic injury and neurodegeneration.
Byrnes
Kimberly R
KR
Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. krb27@georgetown.edu
Loane
David J
DJ
Faden
Alan I
AI
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000627:therapeutic use*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D006801:Humans; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D018094:Receptors, Metabotropic Glutamate