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Ionotropic Receptors in the Central Nervous System and Neurodegenerative Disease

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Abstract

Glutamate was identified as the main excitatory neurotransmitter in the mammalian central nervous system (CNS) following the observation in the early 1950s that glutamate can induce seizure activity and excite neurons in the mammalian brain. Over the last two decades, selective ligands, including competitive agonists and antagonists and allosteric modulators, have been developed to further investigate the functional role of glutaminergic receptors. Glutamate released from synapses can activate ligand-gated cation channels at postsynaptic cells to mediate fast postsynaptic potentials. These ion channel-forming ionotropic glutamate receptors (iGluRs) are divided into N-methyl-d-aspartate (NMDA), α-amino-3-hydroxyl-5-methyl-isoxazole-4-prorionate (AMPA), and kainate (KA) receptors. While only 20–30 % of the amino acid sequence is shared among these receptor subtypes, they share similar structural features and their activity is based on specific pharmacological preference. In this chapter, we will describe the structure and composition of iGluRs and infer their pharmacology, with a particular focus on their role in the CNS and their relevance to the pathogenesis of neurodegenerative diseases.

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References

  • Addae, J. I., Evans, S. M., et al. (2000). NMDA-induced changes in a cortical network in vivo are prevented by AMPA. Brain Research, 869(1–2), 211–215.

    CAS  PubMed  Google Scholar 

  • Alt, A., Weiss, B., et al. (2004). Pharmacological characterisation of glutamatergic agonists and antagonists at recombinant human homomeric and heteromeric kainate receptors in vitro. Neuropharmacology, 46, 793–806.

    CAS  PubMed  Google Scholar 

  • Araki, T., Kumagai, T., et al. (2000). Protective effect of riluzole on MPTP-induced depletion of dopamine and its metabolite content in mice. Metabolic Brain Disease, 15(3), 193–201.

    CAS  PubMed  Google Scholar 

  • Araque, A., Sanzgiri, R. P., et al. (1998). Calcium elevation in astrocytes causes an NMDA receptor-dependent increase in the frequency of miniature synaptic currents in cultured hippocampal neurons. The Journal of Neuroscience, 18(17), 6822–6829.

    CAS  PubMed  Google Scholar 

  • Armstrong, N., Sun, Y., et al. (1998). Structure of a glutamate-receptor ligand binding core in complex with kainate. Nature, 395, 913–917.

    CAS  PubMed  Google Scholar 

  • Bamberger, M. E., & Landreth, G. E. (2001). Microglial interaction with beta-amyloid: Implications for the pathogenesis of Alzheimer’s disease. Microscopy Research and Technique, 54(2), 59–70.

    CAS  PubMed  Google Scholar 

  • Barnum, C., & Tansey, M. (2010). Modeling neuroinflammatory pathogenesis of Parkinson’s disease. Progress in Brain Research, 184, 113–132.

    CAS  PubMed  Google Scholar 

  • Beal, M. F. (2003). Mitochondria, oxidative damage, and inflammation in Parkinson’s disease. Annals of the New York Academy of Sciences, 991, 120–131.

    CAS  PubMed  Google Scholar 

  • Beal, M. F., Kowall, N. W., et al. (1986). Replication of the neurochemical characteristics of Huntington’s disease by quinolinic acid. Nature, 321(6066), 168–171.

    CAS  PubMed  Google Scholar 

  • Beaton, J. A., Stemsrud, K., et al. (1992). Identification of a novel N-methyl-d-aspartate receptor population in the rat medial thalamus. Journal of Neurochemistry, 59(2), 754–757.

    CAS  PubMed  Google Scholar 

  • Bergeron, R., Meyer, T. M., et al. (1998). Modulation of N-methyl-d-aspartate receptor function by glycine transport. Proceedings of the National Academy of Sciences of the United States of America, 95(26), 15730–15734.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Berliocchi, L., Bano, D., et al. (2005). Ca2+ signals and death programmes in neurons. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 360, 2255–2258.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Birch, P., Grossman, C., et al. (1988). 6,7-Dintro-quinoxaline-2,3-dion and 6-nitro,7-cyano-quinoxaline-2,3-dion antagonise responses to NMDA in the rat spinal cord via an action at the strychine-insensitive glycine receptor. European Journal of Pharmacology, 156, 177–180.

    CAS  PubMed  Google Scholar 

  • Bleakman, D., Gates, M., et al. (2002). Kainate receptor agonists, antagonists and allosteric modulators. Current Pharmaceutical Design, 8, 873–885.

    CAS  PubMed  Google Scholar 

  • Blennow, K., de Leon, M. J., et al. (2006). Alzheimer’s disease. Lancet, 368(9533), 387–403.

    CAS  PubMed  Google Scholar 

  • Boillee, S., Vande Velde, C., et al. (2006). ALS: A disease of motor neurons and their nonneuronal neighbors. Neuron, 52(1), 39–59.

    CAS  PubMed  Google Scholar 

  • Boillee, S., Yamanaka, K., et al. (2006). Onset and progression in inherited ALS determined by motor neurons and microglia. Science, 312(5778), 1389–1392.

    CAS  PubMed  Google Scholar 

  • Borges, K., & Dingledine, R. (1998). AMPA receptors: Molecular and functional diversity. Progress in Brain Research, 116, 153–170.

    CAS  PubMed  Google Scholar 

  • Bowie, D., & Mayer, M. (1995). Inward rectification of both AMPA and kainate subtype glutamate receptors generated by polyamine-mediated ion channel block. Neuron, 15, 453–462.

    CAS  PubMed  Google Scholar 

  • Braidy, N., Grant, R., et al. (2009). Mechanism for quinolinic acid cytotoxicity in human astrocytes and neurons. Neurotoxicity Research, 16, 77–86.

    CAS  PubMed  Google Scholar 

  • Bristow, L., Hutson, P., et al. (1996). Anticonvulsant and behavioural profile of L-701,324, a potent, orally active antagonist at the glycine modulatory site on the N-methyl-d-aspartate receptor complex. The Journal of Pharmacology and Experimental Therapeutics, 279, 492–501.

    CAS  PubMed  Google Scholar 

  • Bruyn, R. P., & Stoof, J. C. (1990). The quinolinic acid hypothesis in Huntington’s chorea. Journal of the Neurological Sciences, 95(1), 29–38.

    CAS  PubMed  Google Scholar 

  • Budd, S. L., Tenneti, L., et al. (2000). Mitochondrial and extramitochondrial apoptotic signaling pathways in cerebrocortical neurons. Proceedings of the National Academy of Sciences of the United States of America, 97(11), 6161–6166.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Butterfield, D. A. (1997). β-Amyloid associated free radical oxidative stress and neurotoxicity: Implications for Alzheimer’s disease. Chemical Research in Toxicology, 10, 495–506.

    CAS  PubMed  Google Scholar 

  • Carriedo, S., Yin, H., et al. (1996). Motor neurons are selectively vulnerable to AMPA/kainate receptor-mediated injury in vitro. The Journal of Neuroscience, 16, 4069–4079.

    CAS  PubMed  Google Scholar 

  • Catts, S. V., Ward, P. B., et al. (1997). Molecular biological investigations into the role of the NMDA receptor in the pathophysiology of schizophrenia. The Australian and New Zealand Journal of Psychiatry, 31(1), 17–26.

    CAS  PubMed  Google Scholar 

  • Ceresoli-Borroni, G., Guidetti, P., et al. (1999). Acute and chronic changes in kynurenate formation following an intrastriatal quinolinate injection in rats. Journal of Neural Transmission, 106(3–4), 229–242.

    CAS  PubMed  Google Scholar 

  • Chatterton, J. E., Awobuluyi, M., et al. (2002). Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits. Nature, 415(6873), 793–798.

    CAS  PubMed  Google Scholar 

  • Chen, Q., Harris, C., et al. (1995). Glutamate-mediated excitotoxic death of cultured striated neurons is mediated by non-NMDA receptors. Experimental Neurology, 136, 212–224.

    CAS  PubMed  Google Scholar 

  • Chen, Y., Brew, B. J., et al. (2011). Characterisation of the kynurenine pathway in NSC-34 cell line: Implications for amyotropic lateral sclerosis. Journal of Neurochemistry, 118, 816–825.

    CAS  PubMed  Google Scholar 

  • Christie, J. M., Jane, D. E., et al. (2000). Native N-methyl-d-aspartate receptors containing NR2A and NR2B subunits have pharmacologically distinct competitive antagonist binding sites. The Journal of Pharmacology and Experimental Therapeutics, 292(3), 1169–1174.

    CAS  PubMed  Google Scholar 

  • Clements, J., & Westbrook, G. L. (1991). Activation kinetics reveal the number of glutamate and glycine binding sites on the N-methyl-d-aspartate receptor. Neuron, 7, 606–613.

    Google Scholar 

  • Colwell, C. S., Altemus, K. L., et al. (1996). Regulation of N-methyl-d-aspartate-induced toxicity in the neostriatum: A role for metabotropic glutamate receptors? Proceedings of the National Academy of Sciences of the United States of America, 93(3), 1200–1204.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Comoletti, D., Muzio, V., et al. (2001). Nitric oxide produced by non-motoneuron cells enhances rat embryonic motoneuron sensitivity to excitotoxins: Comparison in mixed neuron/glia or purified cultures. Journal of the Neurological Sciences, 192(1–2), 61–69.

    CAS  PubMed  Google Scholar 

  • Conti, F., DeBiasi, S., et al. (1996). Expression of NR1 and NR2A/B subunits of the NMDA receptor in cortical astrocytes. Glia, 17(3), 254–258.

    CAS  PubMed  Google Scholar 

  • Conti, F., Barbaresi, P., et al. (1999). Neuronal and glial localization of NR1 and NR2A/B subunits of the NMDA receptor in the human cerebral cortex. Cerebral Cortex, 9(2), 110–120.

    CAS  PubMed  Google Scholar 

  • Contractor, A., Swanson, G., et al. (2000). Identification of the kainate receptor subunits underlying modulation of excitatory synaptic transmission in the CA3 region of the hippocampus. The Journal of Neuroscience, 20, 8269–8278.

    CAS  PubMed  Google Scholar 

  • Dannhardt, G., & Kohl, B. K. (1998). The glycine site on the NMDA receptor: Structure-activity relationships and possible therapeutic applications. Current Medicinal Chemistry, 5(4), 253–263.

    CAS  PubMed  Google Scholar 

  • Danysz, W. (2002). CX-516 cortex pharmaceuticals. Current Opinion in Investigational Drugs, 3, 1081–1088.

    CAS  PubMed  Google Scholar 

  • Das, S., Sasaki, Y., et al. (1998). Increased NMDA current and spine density in mice lacking the NMDA receptor subunit NR3A. Nature, 393, 377–381.

    CAS  PubMed  Google Scholar 

  • De Carvalho, L. P., Bochet, P., et al. (1996). The endogenous agonist quinolinic acid and the non endogenous homoquinolinic acid discriminate between NMDAR2 receptor subunits. Neurochemistry International, 28(4), 445–452.

    PubMed  Google Scholar 

  • Dingledine, R., & McBain, C. J. (1994). Excitatory amino acid transmitters. In G. J. Siegel, B. W. Agranoff, & R. W. Albers (Eds.), Basic neurochemistry: Molecular, cellular and medical aspects (pp. 367–387). New York: Raven Press.

    Google Scholar 

  • Dingledine, R., Borges, K., et al. (1999). The glutamate receptor ion channels. Pharmacological Reviews, 51(1), 7–61.

    CAS  PubMed  Google Scholar 

  • Dodd, P. R. (2002). Excited to death: Different ways to lose your neurones. Biogerontology, 3(1–2), 51–56.

    CAS  PubMed  Google Scholar 

  • Doggrell, S. (2003). Is memantine a breakthrough in the treatment of moderate-to-severe Alzheimer’s disease? Expert Opinion on Pharmacotherapy, 4(10), 1857–1860.

    CAS  PubMed  Google Scholar 

  • Ellison, D. W., Beal, M. F., et al. (1987). Amino acid neurotransmitter abnormalities in Huntington’s disease and the quinolinic acid animal model of Huntington’s disease. Brain, 110(Pt 6), 1657–1673.

    PubMed  Google Scholar 

  • Estevez, A., Stutzmann, J., et al. (1995). Protective effect of riluzole on excitatory amino-acid mediated neurotoxicity in motoneurons-enriched cultures. European Journal of Pharmacology, 280, 47–53.

    CAS  PubMed  Google Scholar 

  • Estrada Sanchez, A., Mejia-Toiber, J., et al. (2008). Excitotoxic neuronal death and the pathogenesis of Huntington’s disease. Archives of Medical Research, 39, 265–276.

    CAS  PubMed  Google Scholar 

  • Farlow, M. R. (2004). NMDA receptor antagonists. A new therapeutic approach for Alzheimer’s disease. Geriatrics, 59(6), 22–27.

    PubMed  Google Scholar 

  • Ferrante, R. J., Kowall, N. W., et al. (1993). Excitotoxin lesions in primates as a model for Huntington’s disease: Histopathologic and neurochemical characterization. Experimental Neurology, 119(1), 46–71.

    CAS  PubMed  Google Scholar 

  • Ferris, S. H. (2003). Evaluation of memantine for the treatment of Alzheimer’s disease. Expert Opinion on Pharmacotherapy, 4(12), 2305–2313.

    CAS  PubMed  Google Scholar 

  • Figueredo-Cardenas, G., Anderson, K. D., et al. (1994). Relative survival of striatal projection neurons and interneurons after intrastriatal injection of quinolinic acid in rats. Experimental Neurology, 129(1), 37–56.

    CAS  PubMed  Google Scholar 

  • Finlayson, K., Witchel, H., et al. (2004). Acquired QT interval prolongation and HERG: Implications for drug discovery and development. European Journal of Pharmacology, 500, 129–142.

    CAS  PubMed  Google Scholar 

  • Foster, A. C., Collins, J. F., et al. (1983). On the excitotoxic properties of quinolinic acid, 2,3-piperidine dicarboxylic acids and structurally related compounds. Neuropharmacology, 22(12A), 1331–1342.

    CAS  PubMed  Google Scholar 

  • Foster, A. C., Gill, R., et al. (1987). Systemic administration of MK-801 prevents N-methyl-d-aspartate-induced neuronal degeneration in rat brain. Neuroscience Letters, 76(3), 307–311.

    CAS  PubMed  Google Scholar 

  • Foster, A. C., Gill, R., et al. (1988). Neuroprotective effects of MK-801 in vivo: Selectivity and evidence for delayed degeneration mediated by NMDA receptor activation. The Journal of Neuroscience, 8(12), 4745–4754.

    CAS  PubMed  Google Scholar 

  • Foster, A. C., Kemp, J. A., et al. (1992). Kynurenic acid analogues with improved affinity and selectivity for the glycine site on the N-methyl-d-aspartate receptor from rat brain. Molecular Pharmacology, 41(5), 914–922.

    CAS  PubMed  Google Scholar 

  • Gallarda, T., & Loo, H. (2004). Memantine (Ebixa): A new therapeutic strategy for the treatment of moderate to severe forms of Alzheimer’s disease. Encephale, 30(1), 69–79.

    CAS  PubMed  Google Scholar 

  • Gallyas, F., Ball, S., et al. (2003). Assembly and cell surface expression of KA-2 subunit-containing kainate receptors. Journal of Neurochemistry, 86, 1414–1427.

    CAS  PubMed  Google Scholar 

  • Gardoni, F., & Di Luca, M. (2006). New targets for pharmacological intervention in the glutamatergic synapse. European Journal of Pharmacology, 545(1), 2–10.

    CAS  PubMed  Google Scholar 

  • Geiger, J., Melcher, T., et al. (1995). Relative abundance of subunit mRNAs determines gating and Ca2+ permeability of AMPA receptors in principals neurons and interneurons in rat CNS. Neuron, 15, 193–204.

    CAS  PubMed  Google Scholar 

  • Guillemin, G. J. (2003). Microglial activation. In ANPP (Ed.), Functional neuroanatomy. Microglia (Vol. 7, p. 4.1). Paris: ANPP.

    Google Scholar 

  • Guillemin, G., Smythe, G., et al. (2004). Expression of indoleamine 2,3-dioxygenase and production of quinolinic acid by human microglia, astrocytes and neurons. Glia, 49, 15–23.

    Google Scholar 

  • Guillemin, G. J., Brew, B. J., et al. (2005). Indoleamine 2,3 dioxygenase and quinolinic acid immunoreactivity in Alzheimer’s disease hippocampus. Neuropathology and Applied Neurobiology, 31(4), 395–404.

    CAS  PubMed  Google Scholar 

  • Guillemin, G. J., Brew, B. J. et al. (2007). Mass spectrometric detection of quinolinic acid in microdissected Alzheimer’s disease plaques. International Congress Series, K. Takai. 1304, 404–408.

    CAS  Google Scholar 

  • Gurney, M. E., Fleck, T. J., et al. (1998). Riluzole preserves motor function in a transgenic model of familial amyotrophic lateral sclerosis. Neurology, 50(1), 62–66.

    CAS  PubMed  Google Scholar 

  • Hague, S., Klaffe, S., et al. (2005). Neurodegenerative disorders: Parkinson’s disease and Huntington’s disease. Journal of Neurology, Neurosurgery, and Psychiatry, 76, 1058–1063.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hartley, D. M., Monyer, H., et al. (1990). 7-Chlorokynurenate blocks NMDA receptor-mediated neurotoxicity in murine cortical culture. The European Journal of Neuroscience, 2(4), 291–295.

    PubMed  Google Scholar 

  • Hartmann, T. (1999). Intracellular biology of Alzheimer’s disease amyloid beta peptide. European Archives of Psychiatry and Clinical Neuroscience, 249(6), 291–298.

    CAS  PubMed  Google Scholar 

  • Hertz, L., Dringen, R., et al. (1999). Astrocytes: Glutamate producers for neurons. Journal of Neuroscience Research, 57(4), 417–428.

    CAS  PubMed  Google Scholar 

  • Hollander, D., Pradas, J., et al. (1992). Long-term high dose dextromethorphan in amyotropic lateral sclerosis. Annals of Neurology, 32, 280.

    Google Scholar 

  • Hollander, D., Pradas, J., et al. (1994). High-dose dextromethorphan in amyotropic lateral sclerosis: Phase I safety and pharmacokinetic studies. Annual Review of Neuroscience, 36, 920–924.

    CAS  Google Scholar 

  • Honer, M., Benke, D., et al. (1998). Differentiation of glycine antagonist sites of N-methyl-d-aspartate receptor subtypes. Preferential interaction of CGP 61594 with NR1/2B receptors. The Journal of Biological Chemistry, 273(18), 11158–11163.

    CAS  PubMed  Google Scholar 

  • Hsieh, M., Gu, S., et al. (2012). Effects of MK-801 on recognition and neurodegeneration in an MPTP-induced Parkinson’s disease rat model. Behavioural Brain Research, 229, 41–47.

    CAS  PubMed  Google Scholar 

  • Hugon, J., & Vallet, J. (1990). Abnormal distribution of phosphorylated neurofilaments in neuronal degeneration induced by kainic acid. Neuroscience Letters, 119, 45–48.

    CAS  PubMed  Google Scholar 

  • Hugon, J., Ludolph, A., et al. (1988). Studies on the aetiology and pathogenesis of motor neurons diseases. II. Clincial and electrophysiologica features of pyramidal dysfunction in macaques fed Lathyrus sativus and IDPN. Neurology, 38, 435–442.

    CAS  PubMed  Google Scholar 

  • Hwang, J. Y., Kim, Y. H., et al. (1999). N-Methyl-d-aspartate receptor blockade induces neuronal apoptosis in cortical culture. Experimental Neurology, 159, 124–130.

    CAS  PubMed  Google Scholar 

  • Jane, D. E., Olverman, H., et al. (1994). Agonists and competitive antagonists: Structure activity and molecular modelling studies. In G. L. Collingridge & J. Watkins (Eds.), The NMDA receptor. New York: Oxford University Press.

    Google Scholar 

  • Javitt, D. C., & Zukin, S. (1990). The role of excitatory amino acids in neuropsychiatric illness. The Journal of Neuropsychiatry and Clinical Neurosciences, 2, 44–52.

    CAS  PubMed  Google Scholar 

  • Jhamandas, K. H., Boegman, R. J., et al. (2000). Excitotoxicity of quinolinic acid: Modulation by endogenous antagonists. Neurotoxicity Research, 2(2–3), 139–155.

    CAS  PubMed  Google Scholar 

  • Kato, T. (2004). Memantine: A therapeutic drug for Alzheimer’s disease and the comparison with MK-801. Folia Pharmacologica Japan, 124, 145–151.

    CAS  Google Scholar 

  • Kawamata, J., & Shimohama, S. (2002). Association of novel and established polymorphisms in neuronal nicotinic acetylcholine receptors with sporadic Alzheimer’s disease. Journal of Alzheimer's Disease, 4(2), 71–76.

    CAS  PubMed  Google Scholar 

  • Kemp, J. A., & Leeson, P. (1993). The glycine site of the NMDA receptor – Five years on. Trends in Pharmacological Sciences, 14, 20–25.

    CAS  PubMed  Google Scholar 

  • Kemp, J. A., Foster, A. C., et al. (1988). 7-Chlorokynurenic acid is a selective antagonist at the glycine modulatory site of the N-methyl-d-aspartate receptor. Proceedings of the National Academy of Sciences of the United States of America, 85, 6547–6550.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kerchner, G., Wilding, T., et al. (2002). Kainate receptor subunits underlying presynaptic regulation of transmitter release in the dorsal horn. The Journal of Neuroscience, 22, 8010–8017.

    CAS  PubMed  Google Scholar 

  • Kew, J. N. C., & Kemp, J. A. (2005). Ionotropic and metabotropic glutamate receptor structure and pharmacology. Psychopharmacology, 179, 4–29.

    CAS  PubMed  Google Scholar 

  • Kew, J., Koester, A., et al. (2000). Functional consequences of reduction in NMDA receptor glycine affinity in mice carrying targeted point mutations in the glycine binding site. The Journal of Neuroscience, 20, 4037–4049.

    CAS  PubMed  Google Scholar 

  • Kloda, A., Clements, J., et al. (2004). Adenosine triphosphate acts as both a competitive antagonist and a positive allosteric modulator at recombinant N-methyl-d-aspartate receptors. Molecular Pharmacology, 65, 1386–1396.

    CAS  PubMed  Google Scholar 

  • Lazzaro, J., Paternain, A., et al. (2002). Functional characterisation of CP-465,022, a selective, non-competitive AMAP receptor antagonist. Neuropharmacology, 42, 143–153.

    CAS  PubMed  Google Scholar 

  • Lee, M., Ting, K., et al. (2011). Characterisation of the expression of NMDA receptors in human astrocytes. PloS One, 5(11), e14123.

    Google Scholar 

  • Lerma, J., Paternain, A., et al. (2001). Molecular physiology of kainate receptors. Physiological Reviews, 81, 971–998.

    CAS  PubMed  Google Scholar 

  • Levine, M., Klapstein, G., et al. (1999). Enhanced sensitivity to N-methyl-d-aspartate receptor activation and knockdown mouse models of Huntington’s disease. Journal of Neuroscience Research, 58, 515–532.

    CAS  PubMed  Google Scholar 

  • Liu, S., & Cull-Candy, S. (2002). Activity-dependent change in AMPA receptor properties in cerebellar stellate cells. The Journal of Neuroscience, 22, 3881–3889.

    CAS  PubMed  Google Scholar 

  • Liu, Q., Xu, Q., et al. (2004). Astrocyte-mediated activation of neuronal kainate receptors. Proceedings of the National Academy of Sciences of the United States of America, 101, 3172–3177.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Loftis, J. M., & Janowsky, A. (2003). The N-methyl-d-aspartate receptor subunit NR2B: Localization, functional properties, regulation, and clinical implications. Pharmacology & Therapeutics, 97(1), 55–85.

    CAS  Google Scholar 

  • Luqquin, M., Obeso, J., et al. (1993). The AMPA receptor antagonist NBQX does not alter the motor response induced by selective dopamine agonists in MPTP-treated monkeys. European Journal of Pharmacology, 235, 297–300.

    Google Scholar 

  • Matsuda, K., Fletcher, M., et al. (2003). Specific assembly with the NMDA receptor 3B subunit controls surface expression and calcium permeability of NMDA receptors. The Journal of Neuroscience, 23(31), 10064–10073.

    CAS  PubMed  Google Scholar 

  • Mattson, M. P. (2004). Pathway towards and away from Azheimer’s disease. Nature, 430, 630–639.

    Google Scholar 

  • Mayer, M., & Armstrong, N. (2004). Structure and function of glutamate receptor ion channels. Annual Review of Physiology, 66, 161–181.

    CAS  PubMed  Google Scholar 

  • McBain, C., & Mayer, M. (1994). N-Methyl-d-aspartic acid receptor structure and function. Physiological Reviews, 74, 723–760.

    CAS  PubMed  Google Scholar 

  • Miller, R. G., Mitchell J. D. et al. (2007). Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). The Cochrane Database of Systematic Reviews, (1), CD001447.

    Google Scholar 

  • Monyer, H., Sprengel, R., et al. (1992). Heteromeric NMDA receptors: Molecular and functional distinction of subtypes. Science, 256(5060), 1217–1221.

    CAS  PubMed  Google Scholar 

  • Monyer, H., Burnashev, N., et al. (1994). Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron, 12(3), 529–540.

    CAS  PubMed  Google Scholar 

  • Mosley, R., Benner, E., et al. (2006). Neuroinflammation, oxidative stress, and the pathogenesis of Parkinson’s disease. Clinical Neuroscience Research, 6(5), 261–281.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nakai, M., Qin, Z., et al. (2000). NMDA and non-NMDA receptor-stimulated IkappaB-alpha degradation: Differential effects of the caspase-3 inhibitor DEVD.CHO, ethanol and free radical scavenger OPC-14117. Brain Research, 859(2), 207–216.

    CAS  PubMed  Google Scholar 

  • Nishi, M., Hinds, H., et al. (2001). Motoneuron-specific expression of NR3B, a novel NMDA-type glutamate receptor subunit that works in a dominant-negative manner. The Journal of Neuroscience, 21(23), RC185.

    CAS  PubMed  Google Scholar 

  • Olney, J. W. (1978). Neurotoxicity of excitatory amino acids. In E. G. McGeer, J. W. Olney, & P. L. McGeer (Eds.), Kainic acid as a tool in neurobiology (pp. 95–112). New York: Raven Press.

    Google Scholar 

  • Parameshwaran, K., Dhanasekaran, M., et al. (2008). Amyloid beta peptides and glutamatergic synaptic dysregulation. Experimental Neurology, 210, 7–13.

    CAS  PubMed  Google Scholar 

  • Pierson, J., Norris, J., et al. (2004). Molecular profiling of experimental Parkinson’s disease: Direct analysis of peptides and proteins on brain tissue sections by MALDI mass spectrometry. Journal of Proteome Research, 3(2), 289–295.

    CAS  PubMed  Google Scholar 

  • Priestley, T., Horne, A. L., et al. (1990). The effect of NMDA receptor glycine site antagonists on hypoxia-induced neurodegeneration of rate cortical cell cultures. Brain Research, 531, 183–188.

    CAS  PubMed  Google Scholar 

  • Priestley, T., Ochu, E., et al. (1994). Subtypes of NMDA receptor in neurons cultured from rat brain. NeuroReport, 5, 1763–1765.

    CAS  PubMed  Google Scholar 

  • Priestley, T., Laughton, P., et al. (1995). Pharmacological properties of recombinant human N-methyl-d-aspartate receptors comprising NR1a/NR2A and NR1a/NR2B subunit assemblies expressed in permanently transfected mouse fibroblast cells. Molecular Pharmacology, 48(5), 841–848.

    CAS  PubMed  Google Scholar 

  • Rae, C., Moussa, C. E., et al. (2006). A metabolomic approach to ionotropic glutamate receptor subtype function: A nuclear magnetic resonance in vitro investigation. Journal of Cerebral Blood Flow & Metabolism, 8, 1005–1017.

    Google Scholar 

  • Rahman, A., Ting, K., et al. (2009). The excitotoxin quinolinic acid induces tau phosphorylation in human neurons. PloS One, 4(7), e6344.

    PubMed Central  PubMed  Google Scholar 

  • Roche, K. W., Standley, S., et al. (2001). Molecular determinants of NMDA receptor internalisation. Nature Neuroscience, 4, 794–802.

    CAS  PubMed  Google Scholar 

  • Rogawski, M. A., Gryder, D., et al. (2003). GluR5 kainate receptors, seizures, and the amygdala. Annals of the New York Academy of Sciences, 985, 150–162.

    CAS  PubMed  Google Scholar 

  • Rosenmund, C., Stern-Bach, Y., et al. (1998). The tetrameric structure of a glutamate receptor channel. Science, 280, 1596–1599.

    CAS  PubMed  Google Scholar 

  • Rothstein, J. D. (1995). Excitotoxicity and neurodegeneration in amyotrophic lateral sclerosis. Clinical Neuroscience, 3(6), 348–359.

    PubMed  Google Scholar 

  • Seeburg, P. H., & Hartner, J. (2003). Regulation of ion channel/neurotransmitter receptor function by RNA editing. Current Opinion in Neurobiology, 13, 279–283.

    CAS  PubMed  Google Scholar 

  • Seeburg, P. H., Burnashev, N., et al. (1995). The NMDA receptor channel: Molecular design of a coincidence detector. Recent Progress in Hormone Research, 50, 19–34.

    CAS  PubMed  Google Scholar 

  • Solyom, S., & Tarnawa, I. (2002). Non-competitive AMPA antagonists of 2,3-benzodiazepine type. Current Pharmaceutical Design, 8, 913–939.

    CAS  PubMed  Google Scholar 

  • Stensbol, T., Madsen, U., et al. (2002). The AMPA receptor binding site: Focus on agonists and competitive antagonists. Current Pharmaceutical Design, 8, 857–872.

    CAS  PubMed  Google Scholar 

  • Stewart, G. R., Olney, J. W., et al. (1991). Excitotoxicity in the embryonic chick spinal cord. Annals of Neurology, 30, 758–766.

    CAS  PubMed  Google Scholar 

  • Stone, T. W. (2001). Endogenous neurotoxins from tryptophan. Toxicon, 39(1), 61–73.

    CAS  PubMed  Google Scholar 

  • Sun, Y., Savanenin, A., et al. (2001). Polyglutamine-expanded huntingtin promotes sensitisation of N-methyl-d-aspartate receptors via post-synaptic density 95. The Journal of Biological Chemistry, 276, 24713–24718.

    CAS  PubMed  Google Scholar 

  • Tolle, T., Berthele, A., et al. (1993). The differential expression of NMDA and non-NMDA receptor subunits in the rat spinal cord and periaqueductal gray. The Journal of Neuroscience, 13, 5009–5028.

    CAS  PubMed  Google Scholar 

  • Turski, L., Huth, A., et al. (1998). ZK200775: A phosphonate quinoxalinedione AMPA antagonist for neuroprotection in stroke and trauma. Proceedings of the National Academy of Sciences of the United States of America, 95, 10960–10965.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Williams, T., Day, N., et al. (1997). Calcium permeable AMPA receptors: A molecular basis for selective vulnerability in motor neurone disease. Annals of Neurology, 42, 200–207.

    CAS  PubMed  Google Scholar 

  • Wong, P., Cai, H., et al. (2002). Genetically engineered mouse models of neurodegenerative diseases. Nature Neuroscience, 5, 663–669.

    Google Scholar 

  • Yu, W., Sun, Y., et al. (2011). The PINK1/Parkin pathway regulates mitochondrial dynamics and function in mammalian hippocampal and dopaminergic neurons. Human Molecular Genetics, 20(16), 3227–3240.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang, H., Li, Q., et al. (2008). Full length mutant huntingtin is required for altered Ca2+ signaling and apoptosis of striatal neurons in the YAC mouse model of Huntington’s disease. Neurobiology of Disease, 2008(31), 80–88.

    Google Scholar 

  • Zoccolella, S., Beghi, E., et al. (2007). Riluzole and amyotrophic lateral sclerosis survival: A population-based study in southern Italy. European Journal of Neurology, 14(3), 262–268.

    CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the NHMRC Capacity Building Grant to Prof Perminder Sachdev. Nady Braidy is the recipient of an Alzheimer’s Australia Viertel Foundation Postdoctoral Research Fellowship at the University of New South Wales. We sincerely thank the Rebecca Cooper Medical Research Foundation for ongoing financial support of our research.

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Authors and Affiliations

  1. Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia

    Nady Braidy, Tharusha Jayasena & Perminder Sachdev

  2. School of Medical Sciences, Faculty of Medicine and Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, Australia

    Anne Poljak

  3. St. Vincent’s Centre for Applied Medical Research, St. Vincent’s Hospital, Sydney, Australia

    Gilles J. Guillemin

  4. Neuropharmacology Group, MND and Neurodegenerative Diseases Research Centre, Macquarie University, North Ryde, NSW, Australia

    Gilles J. Guillemin

  5. Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, Australia

    Perminder Sachdev

Authors
  1. Nady Braidy
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  2. Anne Poljak
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  3. Tharusha Jayasena
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  4. Gilles J. Guillemin
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  5. Perminder Sachdev
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Corresponding author

Correspondence to Nady Braidy .

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Editors and Affiliations

  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, Tennessee, USA

    Richard M. Kostrzewa

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Braidy, N., Poljak, A., Jayasena, T., Guillemin, G.J., Sachdev, P. (2014). Ionotropic Receptors in the Central Nervous System and Neurodegenerative Disease. In: Kostrzewa, R. (eds) Handbook of Neurotoxicity. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5836-4_126

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