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The role of group I metabotropic glutamate receptors in neuronal excitotoxicity in alzheimer’s disease

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Abstract

Neurodegenerative diseases such as Huntington’s disease, ischemia, and Alzheimer’s disease (AD) are major causes of death. Recently, metabotropic glutamate receptors (mGluRs), a group of seven-transmembrane-domain proteins that couple to G-proteins, have become of interest for studies of pathogenesis. Group I mGluRs control the levels of second messengers such as inositol 1,4,5-triphosphate (IP3), Ca2+ ions and cAMP. They elicit the release of arachidonic acid via intracellular Ca2+ mobilization from intracellular stores such as mitochondria and endoplasmic reticulum. This facilitates the release of glutamate and could trigger the formation of neurofibrillary tangles, a pathological hallmark of AD. mGluRs regulate neuronal injury and survival, possibly through a series of downstream protein kinase and cysteine protease signaling pathways that affect mitochondrially mediated programmed cell death. They may also play a role in glutamate-induced neuronal death by facilitating Ca2+ mobilization. Hence, mGluRs have become a target for neuroprotective drug development. They represent a pharmacological path to a relatively subtle amelioration of neurotoxicity because they serve a modulatory rather than a direct role in excitatory glutamatergic transmission.

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References

  • Aiba A, M Kano, C Chen, ME Stanton, GD Fox, K Herrup, TA Zwingman and S Tonegawa (1994) Deficient cerebellar long- term depression and impaired motor learning in mGluR1 mutant mice.Cell 79, 377–388.

    Article  PubMed  CAS  Google Scholar 

  • Akiyama H, S Barger, S Barnum, B Bradt, J Bauer, GM Cole, NR Cooper, P Eikelenboom, M Emmerling, BL Fiebich, CE Finch, S Frautschy, WS Griffin, H Hampel, M Hull, G Landreth, L Lue, R Mrak, IR Mackenzie, PL McGeer, MK O’Banion, J Pachter, G Pasinetti, C Plata-Salaman, J Rogers, R Rydel, Y Shen, W Streit, R Strohmeyer, I Tooyoma, FL Van Muiswinkel, R Veerhuis, D Walker, S Webster, B Wegrzyniak, G Wenk and T Wyss-Coray (2000) Inflammation and Alzheimer’s disease.Neurobiol. Aging 21,383–421.

    Article  PubMed  CAS  Google Scholar 

  • Allen JW, S Vicini and AI Faden (2001) Exacerbation of neuronal cell death by activation of group I metabotropic glutamate receptors: role of NMDA receptors and arachidonic acid release.Exp. Neurol. 169, 449–460.

    Article  PubMed  CAS  Google Scholar 

  • Anderson JJ, SP Rao, B Rowe, DR Giracello, G Holtz, DF Chapman, L Tehrani, MJ Bradbury, ND Cosford and MA Varney (2002) [3H]Methoxymethyl-3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine binding to metabotropic glutamate receptor subtype 5 in rodent brain:in vitro andin vivo characterization.J. Pharmacol. Exp. Ther. 303, 1044–1051.

    Article  PubMed  CAS  Google Scholar 

  • Ango F, JP Pin, JC Tu, B Xiao, PF Worley, J Bockaert and L Fagni (2000) Dendritic and axonal targeting of type 5 metabotropic glutamate receptor is regulated by homer1 proteins and neuronal excitation.J. Neurosci. 20, 8710–8716.

    PubMed  CAS  Google Scholar 

  • Ango F, L Prezeau, T Muller, JC Tu, B Xiao, PF Worley, JP Pin, J Bockaert and L Fagni (2001) Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer.Nature 411, 962–965.

    Article  PubMed  CAS  Google Scholar 

  • Ango F, D Robbe, JC Tu, B Xiao, PF Worley, JP Pin, J Bockaert and L Fagni (2002) Homer-dependent cell surface expression of metabotropic glutamate receptor type 5 in neurons.Mol. Cell. Neurosci. 20, 323–329.

    Article  PubMed  CAS  Google Scholar 

  • Aramori I and S Nakanishi (1992) Signal transduction and pharma- cological characteristics of a metabotropic glutamate receptor, mGluR1, in transfected CHO cells.Neuron 8, 757–765.

    Article  PubMed  CAS  Google Scholar 

  • Arias C, F Becerra-Garcia and R Tapia (1998) Glutamic acid and Alzheimer’s disease.Neurobiology (Budapest) 6, 33–43.

    CAS  Google Scholar 

  • Aronica E, F Nicoletti, DF Condorelli and R Balasz (1993) Pharmacological characterization of metabotropic glutamate receptors in cultured cerebellar granule cells.Neurochem. Res. 18, 605–612.

    Article  PubMed  CAS  Google Scholar 

  • Aronica E, MV Catania, J Geurts, B Yankaya and D Troost (2001) Immunohistochemical localization of group I and II metabotropic glutamate receptors in control and amyotrophic lateral sclerosis human spinal cord: upregulation in reactive astrocytes.Neuroscience 105, 509–520.

    Article  PubMed  CAS  Google Scholar 

  • Attarian S and M Amalric (1997) Microinfusion of the metabotropic glutamate receptor agonist 1S,3R-1-aminocyclopentane-1,3- dicarboxylic acid into the nucleus accumbens induces dopamine- dependent locomotor activation in the rat.Eur. J. Neurosci. 9, 809–816.

    Article  PubMed  CAS  Google Scholar 

  • Attucci S, V Carla, G Mannaioni and F Moroni (2001) Activation of type 5 metabotropic glutamate receptors enhances NMDA responses in mice cortical wedges.Br. J. Pharmacol. 132, 799- 806.

    Article  PubMed  CAS  Google Scholar 

  • Bao WL, AJ Williams, AI Faden and FC Tortella (2001) Selective mGluR5 receptor antagonist or agonist provides neuroprotection in a rat model of focal cerebral ischemia.Brain Res. 922, 173- 179.

    Article  PubMed  CAS  Google Scholar 

  • Barger SW, RR Fiscus, P Ruth, F Hofmann and MP Mattson (1995) Role of cyclic GMP in the regulation of neuronal calcium and survival by secreted forms of β-amyloid precursor.J. Neurochem. 64, 2087–2096.

    PubMed  CAS  Google Scholar 

  • Bashir ZI, ZA Bortolotto, CH Davies, N Berretta, AJ Irving, AJ Seal, JM Henley, DE Jane, JC Watkins and GL Collingridge (1993) Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors.Nature 363, 347- 350.

    Article  PubMed  CAS  Google Scholar 

  • Baude A, Z Nusser, JD Roberts, E Mulvihill, RA McIlhinney and P Somogyi (1993) The metabotropic glutamate receptor (mGluR1a) is concentrated at perisynaptic membrane of neuronal subpopulations as detected by immunogold reaction.Neuron 11, 771–787.

    Article  PubMed  CAS  Google Scholar 

  • Bazan NG, V Colangelo and WJ Lukiw (2002) Prostaglandins and other lipid mediators in Alzheimer’s disease.Prostaglandins Other Lipid Mediat. 68-69, 197–210.

    Article  PubMed  Google Scholar 

  • Bear MF and RC Malenka (1994) Synaptic plasticity: LTP and LTD.Curr. Opin. Neurobiol. 4, 389–399.

    Article  PubMed  CAS  Google Scholar 

  • Berthele A, S Platzer, DJ Laurie, S Weis, B Sommer, W Zieglgansberger, B Conrad and TR Tolle (1999) Expression of metabotropic glutamate receptor subtype mRNA (mGluR1-8) in human cerebellum.Neuroreport 10, 3861–3867.

    Article  PubMed  CAS  Google Scholar 

  • Biber K, DJ Laurie, A Berthele, B Sommer, TR Tolle, PJ Gebicke-Harter, D van Calker and HW Boddeke (1999) Expression and signaling of group I metabotropic glutamate receptors in astrocytes and microglia.J. Neurochem. 72, 1671–1680.

    Article  PubMed  CAS  Google Scholar 

  • Bito H, K Deisseroth and RW Tsien (1996) CREB phosphorylation and dephosphorylation: a Ca2+- and stimulus duration-dependent switch for hippocampal gene expression.Cell 87, 1203–1214.

    Article  PubMed  CAS  Google Scholar 

  • Blanchard BJ, VL Thomas and VM Ingram (2002) Mechanism of membrane depolarization caused by the Alzheimer Aβ1-42 peptide.Biochem. Biophys. Res. Commun. 293, 1197–1203.

    Article  PubMed  CAS  Google Scholar 

  • Blumcke I, K Behle, B Malitschek, R Kuhn, T Knopfel, HK Wolf and OD Wiestler (1996) Immunohistochemical distribution of metabotropic glutamate receptor subtypes mGluR1b, mGluR2/3, mGluR4a and mGluR5 in human hippocampus.Brain Res. 736, 217–226.

    Article  PubMed  CAS  Google Scholar 

  • Bordi F and A Ugolini (1999) Group I metabotropic glutamate receptors: implications for brain diseases.Prog. Neurobiol. 59, 55–79.

    Article  PubMed  CAS  Google Scholar 

  • Bortolotto ZA and GL Collingridge (1993) Characterisation of LTP induced by the activation of glutamate metabotropic receptors in area CA1 of the hippocampus.Neuropharmacology 32, 1–9.

    Article  PubMed  CAS  Google Scholar 

  • Bortolotto ZA, ZI Bashir, CH Davies, T Taira, K Kaila and GL Collingridge (1995) Studies on the role of metabotropic glutamate receptors in long-term potentiation: some methodological considerations.J. Neurosci. Methods 59, 19–24.

    Article  PubMed  CAS  Google Scholar 

  • Bowes MP, E Masliah, DA Otero, JA Zivin and T Saitoh (1994) Reduction of neurological damage by a peptide segment of the amyloid β/A4 protein precursor in a rabbit spinal cord ischemia model.Exp. Neurol. 129, 112–119.

    Article  PubMed  CAS  Google Scholar 

  • Brabet I, ML Parmentier, C De Colle, J Bockaert, F Acher and JP Pin (1998) Comparative effect of L-CCG-I, DCG-IV and γ-car- boxy-L-glutamate on all cloned metabotropic glutamate receptor subtypes.Neuropharmacology 37, 1043–1051.

    Article  PubMed  CAS  Google Scholar 

  • Bradley SR, AI Levey, SM Hersch and PJ Conn (1996) Immunocytochemical localization of group III metabotropic glutamate receptors in the hippocampus with subtype-specific antibodies.J. Neurosci. 16, 2044–2056.

    PubMed  CAS  Google Scholar 

  • Brakeman PR, AA Lanahan, R O’Brien, K Roche, CA Barnes, RL Huganir and PF Worley (1997) Homer: a protein that selectively binds metabotropic glutamate receptors.Nature 386, 284–288.

    Article  PubMed  CAS  Google Scholar 

  • Brauner-Osborne H, B Nielsen and P Krogsgaard-Larsen (1998) Molecular pharmacology of homologues of ibotenic acid at cloned metabotropic glutamic acid receptors.Eur. J. Pharmacol. 350, 311–316.

    Article  PubMed  CAS  Google Scholar 

  • Brauner-Osborne H, AA Jensen and P Krogsgaard-Larsen (1999) Interaction of CPCCOEt with a chimeric mGlu1b and calcium sensing receptor.Neuroreport 10, 3923–3925.

    PubMed  CAS  Google Scholar 

  • Brauner-Osborne H, J Egebjerg, EO Nielsen, U Madsen and P Krogsgaard-Larsen (2000) Ligands for glutamate receptors: design and therapeutic prospects.J. Med. Chem. 43, 2609–2645.

    Article  PubMed  CAS  Google Scholar 

  • Breysse N, C Baunez, W Spooren, F Gasparini and M Amalric (2002) Chronic but not acute treatment with a metabotropic glutamate 5 receptor antagonist reverses the akinetic deficits in a rat model of parkinsonism.J. Neurosci. 22, 5669–5678.

    PubMed  CAS  Google Scholar 

  • Bruno V, A Copani, T Knopfel, R Kuhn, G Casabona, P Dell’Albani, DF Condorelli and F Nicoletti (1995) Activation of metabotropic glutamate receptors coupled to inositol phospholipid hydrolysis amplifies NMDA-induced neuronal degeneration in cultured cortical cells.Neuropharmacology 34, 1089–1098.

    Article  PubMed  CAS  Google Scholar 

  • Bruno V, G Battaglia, A Kingston, MJ O’Neill, MV Catania, R Di Grezia and F Nicoletti (1999) Neuroprotective activity of the potent and selective mGlu1a metabotropic glutamate receptor antagonist, (+)-2-methyl-4 carboxyphenylglycine (LY367385): comparison with LY357366, a broader spectrum antagonist with equal affinity for mGlu1a and mGlu5 receptors.Neuropharmacology 38, 199–207.

    Article  PubMed  CAS  Google Scholar 

  • Bruno V, G Battaglia, A Copani, M D’Onofrio, P Di Iorio, A De Blasi, D Melchiorri, PJ Flor and F Nicoletti (2001) Metabotropic glutamate receptor subtypes as targets for neuroprotective drugs.J. Cereb. Blood Flow Metab. 21, 1013–1033.

    Article  PubMed  CAS  Google Scholar 

  • Buisson A and DW Choi (1995) The inhibitory mGluR agonist,S- 4-carboxy-3-hydroxy-phenylglycine selectively attenuates NMDA neurotoxicity and oxygen-glucose deprivation-induced neuronal death.Neuropharmacology 34, 1081–1087.

    Article  PubMed  CAS  Google Scholar 

  • Buisson A, SP Yu and DW Choi (1996) DCG-IV selectively attenuates rapidly triggered NMDA-induced neurotoxicity in cortical neurons.Eur. J. Neurosci. 8, 138–143.

    Article  PubMed  CAS  Google Scholar 

  • Bush AI, WH Pettingell, G Multhaup, M de Paradis, JP Vonsattel, JF Gusella, K Beyreuther, CL Masters and RE Tanzi (1994) Rapid induction of Alzheimer Aβ amyloid formation by zinc.Science 265, 1464–1467.

    Article  PubMed  CAS  Google Scholar 

  • Buxbaum JD, SE Gandy, P Cicchetti, ME Ehrlich, AJ Czernik, RP Fracasso, TV Ramabhadran, AJ Unterbeck and P Greengard (1990) Processing of Alzheimer β/A4 amyloid precursor protein: modulation by agents that regulate protein phosphorylation.Proc. Natl. Acad. Sci. USA 87, 6003–6006.

    Article  PubMed  CAS  Google Scholar 

  • Camon L, P Vives, N de Vera and E Martinez (1998) Seizures and neuronal damage induced in the rat by activation of group I metabotropic glutamate receptors with their selective agonist 3,5-dihydroxyphenylglycine.J. Neurosci. Res. 51, 339–348.

    Article  PubMed  CAS  Google Scholar 

  • Caporaso GL, SE Gandy, JD Buxbaum, TV Ramabhadran and P Greengard (1992) Protein phosphorylation regulates secretion of Alzheimer β/A4 amyloid precursor protein.Proc. Natl. Acad. Sci. USA 89, 3055–3059.

    Article  PubMed  CAS  Google Scholar 

  • Carroll FY, A Stolle, PM Beart, A Voerste, I Brabet, F Mauler, C Joly, H Antonicek, J Bockaert, T Muller, JP Pin and L Prezeau (2001) BAY36-7620: a potent non-competitive mGlu1 receptor antagonist with inverse agonist activity.Mol. Pharmacol. 59, 965–973.

    PubMed  CAS  Google Scholar 

  • Cartmell J and DD Schoepp (2000) Regulation of neurotransmitter release by metabotropic glutamate receptors.J. Neurochem. 75, 889–907.

    Article  PubMed  CAS  Google Scholar 

  • Chandler P, M Pennington, ML Maccecchini, NT Nashed and P Skolnick (1993) Polyamine-like actions of peptides derived from conantokin-G, an N-methyl-D-aspartate (NMDA) antagonist. J.Biol. Chem. 268, 17173–17178.

    CAS  Google Scholar 

  • Chapman AG, PK Yip, JS Yap, LP Quinn, E Tang, JR Harris and BS Meldrum (1999) Anticonvulsant actions of LY 367385 ((+)-2- methyl-4-carboxyphenylglycine) and AIDA ((RS)-1-aminoin- dan-1,5-dicarboxylic acid).Eur. J. Pharmacol. 368, 17–24.

    Article  PubMed  CAS  Google Scholar 

  • Chapman AG, K Nanan, M Williams and BS Meldrum (2000) Anticonvulsant activity of two metabotropic glutamate group I antagonists selective for the mGlu5 receptor: 2-methyl-6- (phenylethynyl)-pyridine (MPEP), and (E)-6-methyl-2-styryl-pyridine(SIB 1893).Neuropharmacology 39, 1567–1574.

    Article  PubMed  CAS  Google Scholar 

  • Choe ES and JQ Wang (2001) Group I metabotropic glutamate receptor activation increases phosphorylation of cAMP response element-binding protein, Elk-1, and extracellular signal-regulated kinases in rat dorsal striatum.Brain Res. Mol. Brain Res. 94, 75–84.

    Article  PubMed  CAS  Google Scholar 

  • Ciruela F, MM Soloviev and RA McIlhinney (1999) Cell surface expression of the metabotropic glutamate receptor type 1 alpha is regulated by the C-terminal tail.FEBS Lett. 448, 91–94.

    Article  PubMed  CAS  Google Scholar 

  • Coccurello R, N Breysse and M Amalric (2004) Simultaneous blockade of adenosine A2A and metabotropic glutamate mGlu5 receptors increase their efficacy in reversing Parkinsonian deficits in rats.Neuropsychopharmacology 29, 1451–1461.

    Article  PubMed  CAS  Google Scholar 

  • Collins DR, RC Smith and SN Davies (1995) Interactions between arachidonic acid and metabotropic glutamate receptors in the induction of synaptic potentiation in the rat hippocampal slice.Eur. J. Pharmacol. 294, 147–154.

    Article  PubMed  CAS  Google Scholar 

  • Conn PJ and JP Pin (1997) Pharmacology and functions of metabotropic glutamate receptors.Annu. Rev. Pharmacol. Toxicol. 37, 205–237.

    Article  PubMed  CAS  Google Scholar 

  • Cosford ND, L Tehrani, J Roppe, E Schweiger, ND Smith, J Anderson, L Bristow, J Brodkin, X Jiang, I McDonald, S Rao, M Washburn and MA Varney (2003) 3-[(2-Methyl-1,3-thiazol-4- yl)ethynyl]-pyridine: a potent and highly selective metabotropic glutamate subtype 5 receptor antagonist with anxiolytic activity.J. Med. Chem. 46, 204–206.

    Article  PubMed  CAS  Google Scholar 

  • Costantino G, A Macchiarulo and R Pellicciari (1999) Modeling of amino-terminal domains of group I metabotropic glutamate receptors: Structural motifs affecting ligand selectivity.J. Med. Chem. 42, 5390–5401.

    Article  PubMed  CAS  Google Scholar 

  • Costantino G, A Macchiarulo and R Pellicciari (2001) Homology model of the closed, functionally active, form of the amino terminal domain of mGlur1.Bioorg. Med. Chem. 9, 847–852.

    Article  PubMed  CAS  Google Scholar 

  • Daggett LP, AI Sacaan, M Akong, SP Rao, SD Hess, C Liaw, A Urrutia, C Jachec, SB Ellis, J Dreessenet al. (1995) Molecular and functional characterization of recombinant human metabotropic glutamate receptor subtype 5.Neuropharmacology 34, 871–886.

    Article  PubMed  CAS  Google Scholar 

  • De Blasi A, PJ Conn, J Pin and F Nicoletti (2001) Molecular determinants of metabotropic glutamate receptor signaling.Trends Pharmacol. Sci. 22, 114–120.

    Article  PubMed  Google Scholar 

  • De Vry J, E Horvath and R Schreiber (2001) Neuroprotective and behavioral effects of the selective metabotropic glutamate mGlu(1) receptor antagonist BAY 36-7620.Eur. J. Pharmacol. 428, 203–214.

    Article  PubMed  Google Scholar 

  • Desai MA, JP Burnett, NG Mayne and DD Schoepp (1995) Cloning and expression of a human metabotropic glutamate receptor 1a: enhanced coupling on co-transfection with a glutamate transporter.Mol. Pharmacol. 48, 648–657.

    PubMed  CAS  Google Scholar 

  • Dodd PR, HL Scott and RI Westphalen (1994) Excitotoxic mechanisms in the pathogenesis of dementia.Neurochem. Int. 25, 203- 219.

    Article  PubMed  CAS  Google Scholar 

  • Doherty A J, MJ Palmer, JM Henley, GL Collingridge and DE Jane (1997) (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) activates mGlu5, but no mGlu1, receptors expressed in CHO cells and potentiates NMDA responses in the hippocampus.Neuropharmacology 36, 265–267.

    Article  PubMed  CAS  Google Scholar 

  • Doherty AJ, V Coutinho, GL Collingridge and JM Henley (1999) Rapid internalization and surface expression of a functional, fluorescently tagged G-protein-coupled glutamate receptor.Biochem.J. 341, 415–422.

    Article  PubMed  CAS  Google Scholar 

  • Donevan SDand RT McCabe (2000) Conantokin G is an NR2B- selective competitive antagonist of N-methyl-D-aspartate receptors.Mol. Pharmacol. 58, 614–623.

    PubMed  CAS  Google Scholar 

  • Faden AI, DM O’Leary, L Fan, WL Bao, PGM Mullins and VA Movsesyan (2001) Selective blockade of the mGluR1 receptor reduces traumatic neuronal injuryin vitro and improves outcome after brain trauma.Exp. Neurol. 167, 435–444.

    Article  PubMed  CAS  Google Scholar 

  • Farber SA, RM Nitsch, JG Schulz and RJ Wurtman (1995) Regulated secretion of β-amyloid precursor protein in rat brain.J. Neurosci. 15, 7442–7451.

    PubMed  CAS  Google Scholar 

  • Fitzjohn SM, AE Kingston, D Lodge and GL Collingridge (1999) DHPG-induced LTD in area CA1 of juvenile rat hippocampus; characterisation and sensitivity to novel mGlu receptor antagonists.Neuropharmacology 38, 1577–1583.

    Article  PubMed  CAS  Google Scholar 

  • Flor PJ, K Lindauer, I Puttner, D Ruegg, S Lukic, T Knopfel and R Kuhn (1995) Molecular cloning, functional expression and pharmacological characterization of the human metabotropic glutamate receptor type 2.Eur. J. Neurosci. 7, 622–629.

    Article  PubMed  CAS  Google Scholar 

  • Flor PJ, H Van Der Putten, D Ruegg, S Lukic, T Leonhardt, M Bence, G Sansig, T Knopfel and R Kuhn (1997) A novel splice variant of a metabotropic glutamate receptor, human mGluR7b.Neuropharmacology 36, 153–159.

    Article  PubMed  CAS  Google Scholar 

  • Fonnum F, T Myhrer, RE Paulsen, K Wangen and AR Oksengard (1995) Role of glutamate and glutamate receptors in memory function and Alzheimer’s disease.Ann. NY Acad. Sci. 757, 475- 486.

    Article  PubMed  CAS  Google Scholar 

  • Friberg IK, AB Young and DG Standaert (1998) Differential localization of the mRNAs for the pertussis toxin insensitive G-protein a sub-units Gq, G11, and Gz in the rat brain, and regulation of their expression after striatal deafferentation.Brain Res. Mol. Brain Res. 54, 298–310.

    Article  PubMed  CAS  Google Scholar 

  • Furukawa K and MP Mattson (1998) Secreted amyloid precursor protein a selectively suppresses N-methyl-D-aspartate currents in hippocampal neurons: involvement of cyclic GMP.Neuroscience 83, 429–438.

    Article  PubMed  CAS  Google Scholar 

  • Galvez T, ML Parmentier, C Joly, B Malitschek, K Kaupmann, R Kuhn, H Bittiger, W Froestl, B Bettler and JP Pin (1999) Mutagenesis and modeling of the GABAB receptor extracellular domain support a venus flytrap mechanism for ligand binding.J. Biol. Chem. 274, 13362–13369.

    Article  PubMed  CAS  Google Scholar 

  • Gasparini F, K Lingenhohl, N Stoehr, PJ Flor, M Heinrich, I Vranesic, M Biollaz, H Allgeier, R Heckendorn, S Urwyler, MA Varney, EC Johnson, SD Hess, SP Rao, AI Sacaan, EM Santori, G Velicelebi and R Kuhn (1999) 2-Methyl-6-(phenylethynyl)- pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist.Neuropharmacology 38, 1493–1503.

    Article  PubMed  CAS  Google Scholar 

  • Gasparini F, P Floersheim, PJ Flor, M Heinrich, W Inderbitzin, D Ott, A Pagano, C Stierlin, N Stoehr, I Vranesic and R Kuhn (2001) Discovery and characterization of non-competitive antagonists of group I metabotropic glutamate receptors.Farmaco 56, 95–99.

    Article  PubMed  CAS  Google Scholar 

  • Gasparini F, R Kuhn and JP Pin (2002) Allosteric modulators of group I metabotropic glutamate receptors: novel subtype-selective ligands and therapeutic perspectives.Curr. Opin. Pharmacol. 2, 43–49.

    Article  PubMed  CAS  Google Scholar 

  • Gomeza J, C Joly, R Kuhn, T Knopfel, J Bockaert and JP Pin (1996) The second intracellular loop of metabotropic glutamate receptor 1 cooperates with the other intracellular domains to control coupling to G-proteins.J. Biol. Chem. 271, 2199–2205.

    Article  PubMed  CAS  Google Scholar 

  • Gong QZ, TM Delahunty, RJ Hamm and BG Lyeth (1995) Metabotropic glutamate antagonist, MCPG, treatment of traumatic brain injury in rats.Brain Res. 700, 299–302.

    Article  PubMed  CAS  Google Scholar 

  • Greenamyre JT and AB Young (1989) Excitatory amino acids and Alzheimer’s disease.Neurobiol. Aging 10, 593–602.

    Article  PubMed  CAS  Google Scholar 

  • Greenberg SM, EH Koo, DJ Selkoe, WQ Qiu and KS Kosik (1994) Secreted β-amyloid precursor protein stimulates mitogen-activat- ed protein kinase and enhancestau phosphorylation.Proc. Natl. Acad. Sci. USA 91, 7104–7108.

    Article  PubMed  CAS  Google Scholar 

  • Greenberg SM, WQ Qiu, DJ Selkoe, A Ben-Itzhak and KS Kosik (1995) Amino-terminal region of the β-amyloid precursor protein activates mitogen-activated protein kinase.Neurosci. Lett. 198, 52–56.

    Article  PubMed  CAS  Google Scholar 

  • Haack JA, J Rivier, TN Parks, EE Mena, LJ Cruz and BM Olivera (1990) Conantokin-T. A γ-carboxyglutamate containing peptide with N-methyl-D-aspartate antagonist activity.J. Biol. Chem. 265, 6025–6029.

    PubMed  CAS  Google Scholar 

  • Haass C, AY Hung, MG Schlossmacher, DB Teplow and DJ Selkoe (1993) β-Amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms.J. Biol. Chem. 268, 3021–3024.

    PubMed  CAS  Google Scholar 

  • Hammerland LG, BM Olivera and D Yoshikami (1992) Conantokin-G selectively inhibits N-methyl-D-aspartate-induced currents inXenopus oocytes injected with mouse brain mRNA.Eur. J. Pharmacol. 226, 239–244.

    Article  PubMed  CAS  Google Scholar 

  • Hermans E and RA Challiss (2001) Structural, signalling and regulatory properties of the group I metabotropic glutamate receptors: prototypic family C G-protein-coupled receptors.Biochem. J. 359, 465–484.

    Article  PubMed  CAS  Google Scholar 

  • Herrero I, MT Miras-Portugal and J Sanchez-Prieto (1992) Positive feedback of glutamate exocytosis by metabotropic presynaptic receptor stimulation.Nature 360, 163–166.

    Article  PubMed  CAS  Google Scholar 

  • Herrero I, MT Miras-Portugal and J Sanchez-Prieto (1994) Rapid desensitization of the metabotropic glutamate receptor that facilitates glutamate release in rat cerebrocortical nerve terminals.Eur. J. Neurosci. 6, 115–120.

    Article  PubMed  CAS  Google Scholar 

  • Herrero I, MT Miras-Portugal and J Sanchez-Prieto (1998) Functional switch from facilitation to inhibition in the control of glutamate release by metabotropic glutamate receptors.J. Biol. Chem. 273, 1951–1958.

    Article  PubMed  CAS  Google Scholar 

  • Hisatsune C, H Umemori, M Mishina and T Yamamoto (1999) Phosphorylation-dependent interaction of the N-methyl-D-aspar- tate receptor e2 subunit with phosphatidylinositol 3-kinase.Genes Cells 4, 657–666.

    Article  PubMed  CAS  Google Scholar 

  • Houamed KM, JL Kuijper, TL Gilbert, BA Haldeman, PJ O’Hara, ER Mulvihill, W Almers and FS Hagen (1991) Cloning, expression, and gene structure of a G protein-coupled glutamate receptor from rat brain.Science 252, 1318–1321.

    Article  PubMed  CAS  Google Scholar 

  • Hsu KS, CC Huang and PC Lyu (1996) Inhibition of calcium channels in rat hippocampal CA1 neurons by conantokin-T.Neurosci. Lett. 220, 113–116.

    Article  PubMed  CAS  Google Scholar 

  • Hudspith MJ (1997) Glutamate: a role in normal brain function, anaesthesia, analgesia and CNS injury.Br. J. Anœsth. 78, 731–747.

    CAS  Google Scholar 

  • Hynd MR, HL Scott and PR Dodd (2004) Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer’s disease.Neurochem. Int. 45, 583–595.

    Article  PubMed  CAS  Google Scholar 

  • Ishiguro M, I Ohsawa, C Takamura, T Morimoto and S Kohsaka (1998) Secreted form of β-amyloid precursor protein activates protein kinase C and phospholipase Cγ1 in cultured embryonic rat neocortical cells.Brain Res. Mol. Brain Res. 53, 24–32.

    Article  PubMed  CAS  Google Scholar 

  • Ito I, A Kohda, S Tanabe, E Hirose, M Hayashi, S Mitsunaga and H Sugiyama (1992) 3,5-Dihydroxyphenyl-glycine: a potent agonist of metabotropic glutamate receptors.Neuroreport 3, 1013–1016.

    Article  PubMed  CAS  Google Scholar 

  • Izumi Y, AR Zarrin and CF Zorumski (2000) Arachidonic acid rescues hippocampal long-term potentiation blocked by group I metabotropic glutamate receptor antagonists.Neuroscience 100, 485–491.

    Article  PubMed  CAS  Google Scholar 

  • Jarrett JT and PT Lansbury Jr (1993) Seeding “one-dimensional crystallization” of amyloid: a pathogenic mechanism in Alzheimer’s disease and scrapie?Cell 73, 1055–1058.

    Article  PubMed  CAS  Google Scholar 

  • Johnson CM, CS Hill, S Chawla, R Treisman and H Bading (1997) Calcium controls gene expressionvia three distinct pathways that can function independently of the Ras/mitogen-activated protein kinases (ERKs) signaling cascade.J. Neurosci. 17, 6189–6202.

    PubMed  CAS  Google Scholar 

  • Joly C, J Gomeza, I Brabet, K Curry, J Bockaert and JP Pin (1995) Molecular, functional, and pharmacological characterization of the metabotropic glutamate receptor type 5 splice variants: comparison with mGluR1.J. Neurosci. 15, 3970–3981.

    PubMed  CAS  Google Scholar 

  • Kang J, HG Lemaire, A Unterbeck, JM Salbaum, CL Masters, KH Grzeschik, G Multhaup, K Beyreuther and B Muller-Hill (1987) The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor.Nature 325, 733–736.

    Article  PubMed  CAS  Google Scholar 

  • Kelly JW and WE Balch (2003) Amyloid as a natural product.J. Cell. Biol. 161,461–463.

    Article  PubMed  CAS  Google Scholar 

  • Kingston AE, MJ O’Neill, A Bond, V Bruno, G Battaglia, F Nicoletti, JR Harris, BP Clark, JA Monn, D Lodge and DD Schoepp (1999) Neuroprotective actions of novel and potent ligands of group I and group II metabotropic glutamate receptors.Ann. NY Acad. Sci. 890, 438–449.

    Article  PubMed  CAS  Google Scholar 

  • Kinoshita A, H Ohishi, S Nomura, R Shigemoto, S Nakanishi and N Mizuno (1996) Presynaptic localization of a metabotropic glutamate receptor, mGluR4a, in the cerebellar cortex: a light and electron microscope study in the rat.Neurosci. Lett. 207, 199- 202.

    Article  PubMed  CAS  Google Scholar 

  • Koizumi S, M Ishiguro, I Ohsawa, T Morimoto, C Takamura, K Inoue and S Kohsaka (1998) The effect of a secreted form of β- amyloid-precursor protein on intracellular Ca2+ increase in rat cultured hippocampal neurones.Br. J. Pharmacol. 123, 1483- 1489.

    Article  PubMed  CAS  Google Scholar 

  • Kunishima N, Y Shimada, Y Tsuji, T Sato, M Yamamoto, T Kumasaka, S Nakanishi, H Jingami and K Morikawa (2000) Structural basis of glutamate recognition by a dimeric metabotropic glutamate receptor.Nature 407, 971–977.

    Article  PubMed  CAS  Google Scholar 

  • Kuo YM, MR Emmerling, C Vigo-Pelfrey, TC Kasunic, JB Kirkpatrick, GH Murdoch, MJ Ball and AE Roher (1996) Watersoluble Aβ (N-40, N-42) oligomers in normal and Alzheimer disease brains.J. Biol. Chem. 271, 4077–4081.

    Article  PubMed  CAS  Google Scholar 

  • Lan JY, VA Skeberdis, T Jover, X Zheng, MV Bennett and RS Zukin (2001) Activation of metabotropic glutamate receptor 1 accelerates NMDA receptor trafficking.J. Neurosci. 21, 6058- 6068.

    PubMed  CAS  Google Scholar 

  • Lee RK and RJ Wurtman (1997) Metabotropic glutamate receptors increase amyloid precursor protein processing in astrocytes: inhibition by cyclic AMP.J. Neurochem. 68, 1830–1835.

    PubMed  CAS  Google Scholar 

  • Leist M and P Nicotera (1998a) Apoptosis, excitotoxicity, and neuropathology.Exp. Cell. Res. 239, 183–201.

    Article  PubMed  CAS  Google Scholar 

  • Leist M and P Nicotera (1998b) Calcium and neuronal death.Rev. Physiol. Biochem. Pharmacol. 132, 79–125.

    Article  PubMed  CAS  Google Scholar 

  • Lu YM, Z Jia, C Janus, JT Henderson, R Gerlai, JM Wojtowicz and JC Roder (1997) Mice lacking metabotropic glutamate receptor 5 show impaired learning and reduced CA1 long-term potentiation (LTP) but normal CA3 LTP.J. Neurosci. 17, 5196–5205.

    PubMed  CAS  Google Scholar 

  • Lujan R, Z Nusser, JD Roberts, R Shigemoto and P Somogyi (1996) Perisynaptic location of metabotropic glutamate receptors mGluR1 and mGluR5 on dendrites and dendritic spines in the rat hippocampus.Eur. J. Neurosci. 8, 1488–1500.

    Article  PubMed  CAS  Google Scholar 

  • Lujan R, JDB Roberts, R Shigemoto, H Ohishi and P Somogyi (1997) Differential plasma membrane distribution of metabotropic glutamate receptors mGluR1a, mGluR2 and mGluR5, relative to neurotransmitter release sites.J. Chem. Neuroanat. 13, 219–241.

    Article  PubMed  CAS  Google Scholar 

  • Luo Y and ML Vallano (1995) Arachidonic acid, but not sodium nitroprusside, stimulates presynaptic protein kinase C and phosphorylation of GAP-43 in rat hippocampal slices and synaptosomes.J. Neurochem. 64, 1808–1818.

    PubMed  CAS  Google Scholar 

  • Mailleux P, F Mitchell, JJ Vanderhaeghen, G Milligan and C Erneux (1992) Immunohistochemical distribution of neurons containing the G-proteins Gqa/G11a in the adult rat brain.Neuroscience 51, 311–316.

    Article  PubMed  CAS  Google Scholar 

  • Makoff AJ, T Phillips, C Pilling and P Emson (1997) Expression of a novel splice variant of human mGluR1 in the cerebellum.Neuroreport 8, 2943–2947.

    Article  PubMed  CAS  Google Scholar 

  • Malherbe P, JN Kew, JG Richards, F Knoflach, C Kratzeisen, MT Zenner, RL Faull, JA Kemp and V Mutel (2002) Identification and characterization of a novel splice variant of the metabotropic glutamate receptor 5 gene in human hippocampus and cerebellum.Brain Res. Mol. Brain Res. 109, 168–178.

    Article  PubMed  CAS  Google Scholar 

  • Manahan-Vaughan D and KH Braunewell (1999) Novelty acquisition is associated with induction of hippocampal long-term depression.Proc. Natl. Acad. Sci. USA 96, 8739–8744.

    Article  PubMed  CAS  Google Scholar 

  • Manev RM, N Gabellini and H Manev (1993) Polyamines modulate the function of transfected glutamate receptor mGluR1a.Neuroreport 4, 830–832.

    Article  PubMed  CAS  Google Scholar 

  • Martin LJ, CD Blackstone, RL Huganir and DL Price (1992) Cellular localization of a metabotropic glutamate receptor in rat brain.Neuron 9, 259–270.

    Article  PubMed  CAS  Google Scholar 

  • Mary S, D Stephan, J Gomeza, J Bockaert, RM Pruss and JP Pin (1997) The rat mGlu1d receptor splice variant shares functional properties with the other short isoforms of mGlu1 receptor.Eur. J. Pharmacol. 335, 65–72.

    Article  PubMed  CAS  Google Scholar 

  • Masu M, Y Tanabe, K Tsuchida, R Shigemoto and S Nakanishi (1991) Sequence and expression of a metabotropic glutamate receptor.Nature 349, 760–765.

    Article  PubMed  CAS  Google Scholar 

  • Mattson MP (1994) Secreted forms of β-amyloid precursor protein modulate dendrite outgrowth and calcium responses to glutamate in cultured embryonic hippocampal neurons.J. Neurobiol. 25, 439–450.

    Article  PubMed  CAS  Google Scholar 

  • Mattson MP, B Cheng, AR Culwell, FS Esch, I Lieberburg and RE Rydel (1993a) Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of the β-amyloid precursor protein.Neuron 10, 243–254.

    Article  PubMed  CAS  Google Scholar 

  • Mattson MP, KJ Tomaselli and RE Rydel (1993b) Calcium-destabilizing and neurodegenerative effects of aggregated β-amyloid peptide are attenuated by basic FGF.Brain Res. 621, 35–49.

    Article  PubMed  CAS  Google Scholar 

  • Mattson MP, SW Barger, K Furukawa, AJ Bruce, T Wyss-Coray, RJ Mark and L Mucke (1997) Cellular signaling roles of TGFβ, TNFβ and βAPP in brain injury responses and Alzheimer’s disease.Brain Res. Brain Res. Rev. 23, 47–61.

    Article  PubMed  CAS  Google Scholar 

  • McDonald JW and DD Schoepp (1992) The metabotropic excitatory amino acid receptor agonist 1S,3R-ACPD selectively potentiates N-methyl-D-aspartate-induced brain injury.Eur. J. Pharmacol. 215, 353–354.

    Article  PubMed  CAS  Google Scholar 

  • McGeer PL, M Schulzer and EG McGeer (1996) Arthritis and antiinflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies.Neurology 47, 425–432.

    PubMed  CAS  Google Scholar 

  • McIntosh JM, BM Olivera, LJ Cruz and WR Gray (1984) γ-car- boxyglutamate in a neuroactive toxin.J. Biol. Chem. 259, 14343- 14346.

    PubMed  CAS  Google Scholar 

  • Meldrum BS (1994) The role of glutamate in epilepsy and other CNS disorders.Neurology 44, S14-S23.

    Article  PubMed  CAS  Google Scholar 

  • Mena EE, MF Gullak, MJ Pagnozzi, KE Richter, J Rivier, LJ Cruz and BM Olivera (1990) Conantokin-G: a novel peptide antagonist to the N-methyl-D-aspartic acid (NMDA) receptor.Neurosci. Lett. 118, 241–244.

    Article  PubMed  CAS  Google Scholar 

  • Mills J and PB Reiner (1999) Regulation of amyloid precursor protein cleavage.J. Neurochem. 72, 443–460.

    Article  PubMed  CAS  Google Scholar 

  • Minakami R, F Katsuki and H Sugiyama (1993) A variant of metabotropic glutamate receptor subtype 5: an evolutionally conserved insertion with no termination codon.Biochem. Biophys. Res. Commun. 194, 622–627.

    Article  PubMed  CAS  Google Scholar 

  • Minakami R, F Katsuki, T Yamamoto, K Nakamura and H Sugiyama (1994) Molecular cloning and the functional expression of two isoforms of human metabotropic glutamate receptor subtype5. Biochem. Biophys. Res. Commun. 199, 1136–1143.

    Article  CAS  Google Scholar 

  • Mineff E and J Valtschanoff (1999) Metabotropic glutamate receptors 2 and 3 expressed by astrocytes in rat ventrobasal thalamus.Neurosci. Lett. 270, 95–98.

    Article  PubMed  CAS  Google Scholar 

  • Moechars D, K Lorent, B De Strooper, I Dewachter and F Van Leuven (1996) Expression in brain of amyloid precursor protein mutated in the α-secretase site causes disturbed behavior, neuronal degeneration and premature death in transgenic mice.EMBOJ. 15, 1265–1274.

    CAS  Google Scholar 

  • Moldrich RX and PM Beart (2003) Emerging signalling and protein interactions mediatedvia metabotropic glutamate receptors.Curr. Drug Targets CNS Neurol. Disord. 2, 109–122.

    Article  PubMed  CAS  Google Scholar 

  • Monaghan DT, RJ Bridges and CW Cotman (1989) The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system.Annu. Rev. Pharmacol. Toxicol. 29, 365–402.

    Article  PubMed  CAS  Google Scholar 

  • Montminy MR, GA Gonzalez and KK Yamamoto (1990) Regulation of cAMP-inducible genes by CREB.Trends Neurosci. 13, 184–188.

    Article  PubMed  CAS  Google Scholar 

  • Morrison LD and SJ Kish (1995) Brain polyamine levels are altered in Alzheimer’s disease.Neurosci. Lett. 197, 5–8.

    Article  PubMed  CAS  Google Scholar 

  • Muller U, N Cristina, ZW Li, DP Wolfer, HP Lipp, T Rulicke, S Brandner, A Aguzzi and C Weissmann (1994) Behavioral and anatomical deficits in mice homozygous for a modified β-amyloid precursor protein gene.Cell 79, 755–765.

    Article  PubMed  CAS  Google Scholar 

  • Nakanishi S (1992a) Molecular diversity of glutamate receptors and implications for brain function.Science 258, 597–603.

    Article  PubMed  CAS  Google Scholar 

  • Nakanishi S (1992b) Molecular diversity of the glutamate receptors.Clin. Neuropharmacol. 15 Suppl 1 Pt A, 4A-5A.

    PubMed  Google Scholar 

  • Nakanishi S (1994) Metabotropic glutamate receptors: synaptic transmission, modulation, and plasticity.Neuron 13, 1031–1037.

    Article  PubMed  CAS  Google Scholar 

  • Nakanishi S, M Masu, Y Bessho, Y Nakajima, Y Hayashi and R Shigemoto (1994) Molecular diversity of glutamate receptors and their physiological functions.EXS 71, 71–80.

    PubMed  CAS  Google Scholar 

  • Nakanishi S, Y Nakajima, M Masu, Y Ueda, K Nakahara, D Watanabe, S Yamaguchi, S Kawabata and M Okada (1998) Glutamate receptors: brain function and signal transduction.Brain Res. Brain Res. Rev. 26, 230–235.

    Article  PubMed  Google Scholar 

  • Negyessy L, Z Vidnyanszky, R Kuhn, T Knopfel, TJ Gorcs and J Hamori (1997) Light and electron microscopic demonstration of mGluR5 metabotropic glutamate receptor immunoreactive neuronal elements in the rat cerebellar cortex.J. Comp. Neurol. 385, 641–650.

    Article  PubMed  CAS  Google Scholar 

  • Newsholme P, J Procopio, MM Lima, TC Pithon-Curi and R Curi (2003) Glutamine and glutamate — their central role in cell metabolism and function.Cell. Biochem. Funct. 21, 1–9.

    Article  PubMed  CAS  Google Scholar 

  • Nicoletti F, V Bruno, A Copani, G Casabona and T Knopfel (1996) Metabotropic glutamate receptors: a new target for the therapy of neurodegenerative disorders?Trends Neurosci. 19, 267–271.

    Article  PubMed  CAS  Google Scholar 

  • Nitsch RM, SA Farber, JH Growdon and RJ Wurtman (1993) Release of amyloid β-protein precursor derivatives by electrical depolarization of rat hippocampal slices.Proc. Natl. Acad. Sci. USA 90, 5191–5193.

    Article  PubMed  CAS  Google Scholar 

  • Nitsch RM, A Deng, RJ Wurtman and JH Growdon (1997) Metabotropic glutamate receptor subtype mGluR1a stimulates the secretion of the amyloid β-protein precursor ectodomain. J.Neurochem. 69, 704–712.

    Article  CAS  Google Scholar 

  • Nusser Z, E Mulvihill, P Streit and P Somogyi (1994) Subsynaptic segregation of metabotropic and ionotropic glutamate receptors as revealed by immunogold localization.Neuroscience 61, 421- 427.

    Article  PubMed  CAS  Google Scholar 

  • O’Brien JA, W Lemaire, TB Chen, RS Chang, MA Jacobson, SN Ha, CW Lindsley, HJ Schaffhauser, C Sur, DJ Pettibone, PJ Conn and DL Williams Jr (2003) A family of highly selective allosteric modulators of the metabotropic glutamate receptor subtype 5.Mol. Pharmacol. 64, 731–740.

    Article  PubMed  CAS  Google Scholar 

  • O’Hara PJ, PO Sheppard, H Thogersen, D Venezia, BA Haldeman, V McGrane, KM Houamed, C Thomsen, TL Gilbert and ER Mulvihill (1993) The ligand-binding domain in metabotropic glutamate receptors is related to bacterial periplasmic binding proteins.Neuron 11, 41–52.

    Article  PubMed  CAS  Google Scholar 

  • Ohishi H, R Ogawa-Meguro, R Shigemoto, T Kaneko, S Nakanishi and N Mizuno (1994) Immunohistochemical localization of metabotropic glutamate receptors, mGluR2 and mGluR3, in rat cerebellar cortex.Neuron 13, 55–66.

    Article  PubMed  CAS  Google Scholar 

  • O’Leary DM, V Movsesyan, S Vicini and AI Faden (2000) Selective mGluR5 antagonists MPEP and SIB-1893 decrease NMDA or glutamate-mediated neuronal toxicity through actions that reflect NMDA receptor antagonism.Br. J. Pharmacol. 131, 1429–1437.

    Article  PubMed  CAS  Google Scholar 

  • Olivera BM, WR Gray, R Zeikus, JM McIntosh, J Varga, J Rivier, V de Santos and LJ Cruz (1985) Peptide neurotoxins from fish- hunting cone snails.Science 230, 1338–1343.

    Article  PubMed  CAS  Google Scholar 

  • Orlando LR, SA Alsdorf, JB Penney Jr and AB Young (2001) The role of group I and group II metabotropic glutamate receptors in modulation of striatal NMDA and quinolinic acid toxicity.Exp. Neurol. 167, 196–204.

    Article  PubMed  CAS  Google Scholar 

  • Otani S, N Auclair, JM Desce, MP Roisin and F Crepel (1999) Dopamine receptors and groups I and II mGluRs cooperate for long-term depression induction in rat prefrontal cortex through converging postsynaptic activation of MAP kinases.J. Neurosci. 19, 9788–9802.

    PubMed  CAS  Google Scholar 

  • Ottersen OP and AS Landsend (1997) Organization of glutamate receptors at the synapse.Eur. J. Neurosci. 9, 2219–2224.

    Article  PubMed  CAS  Google Scholar 

  • Palmer E, DT Monaghan and CW Cotman (1988) Glutamate receptors and phosphoinositide metabolism: stimulationvia quisqualate receptors is inhibited by N-methyl-D-aspartate receptor activation.Brain Res. 464, 161–165.

    PubMed  CAS  Google Scholar 

  • Pellegrini-Giampietro DE, F Peruginelli, E Meli, A Cozzi, S Albani-Torregrossa, R Pellicciari and F Moroni (1999) Protection with metabotropic glutamate 1 receptor antagonists in models of ischemic neuronal death: time-course and mechanisms.Neuropharmacology 38, 1607–1619.

    Article  PubMed  CAS  Google Scholar 

  • Pellicciari R, R Luneia, G Costantino, M Marinozzi, B Natalini, P Jakobsen, A Kanstrup, G Lombardi, F Moroni and C Thomsen (1995) 1-Aminoindan-1,5-dicarboxylic acid: a novel antagonist at phospholipase C-linked metabotropic glutamate receptors.J. Med.Chem. 38, 3717–3719.

    Article  PubMed  CAS  Google Scholar 

  • Pellicciari R, M Raimondo, M Marinozzi, B Natalini, G Costantino and C Thomsen (1996) (S)-(+)-2-(3′-carboxybicyclo[1.1.1]pentyl)glycine, a structurally new group I metabotropic glutamate receptor antagonist.J. Med. Chem. 39, 2874–2876.

    Article  PubMed  CAS  Google Scholar 

  • Petralia RS, YX Wang, AS Niedzielski and RJ Wenthold (1996) The metabotropic glutamate receptors, mGluR2 and mGluR3, show unique postsynaptic, presynaptic and glial localizations.Neuroscience 71, 949–976.

    Article  PubMed  CAS  Google Scholar 

  • Petralia RS, YX Wang, S Singh, C Wu, L Shi, J Wei and RJ Wenthold (1997) A monoclonal antibody shows discrete cellular and subcellular localizations of mGluR1a metabotropic gluta- mate receptors.J. Chem. Neuroanat. 13, 77–93.

    Article  PubMed  CAS  Google Scholar 

  • Phillips T, S Rees, S Augood, H Waldvogel, R Faull, C Svendsen and P Emson (2000) Localization of metabotropic glutamate receptor type 2 in the human brain.Neuroscience 95, 1139–1156.

    Article  PubMed  CAS  Google Scholar 

  • Pike CJ, R Balazs and CW Cotman (1996) Attenuation of β-amyloid neurotoxicity in vitro by potassium-induced depolarization.J. Neurochem. 67, 1774–1777.

    PubMed  CAS  Google Scholar 

  • Pin JP and F Acher (2002) The metabotropic glutamate receptors: structure, activation mechanism and pharmacology.Curr. Drug Target CNS Neurol. Disord. 1, 297–317.

    Article  CAS  Google Scholar 

  • Pin JP and J Bockaert (1995) Get receptive to metabotropic glutamate receptors.Curr. Opin. Neurobiol. 5, 342–349.

    Article  PubMed  CAS  Google Scholar 

  • Pin JP and R Duvoisin (1995) The metabotropic glutamate receptors: structure and functions.Neuropharmacology 34, 1–26.

    Article  PubMed  CAS  Google Scholar 

  • Pin JP, C De Colle, AS Bessis and F Acher (1999) New perspectives for the development of selective metabotropic glutamate receptor ligands.Eur. J. Pharmacol. 375, 277–294.

    Article  PubMed  CAS  Google Scholar 

  • Pisani A, P Calabresi, D Centonze and G Bernardi (1997) Enhancement of NMDA responses by group I metabotropic glutamate receptor activation in striatal neurones.Br. J. Pharmacol. 120, 1007–1014.

    Article  PubMed  CAS  Google Scholar 

  • Pisani A, P Gubellini, P Bonsi, F Conquet, B Picconi, D Centonze, G Bernardi and P Calabresi (2001) Metabotropic glutamate receptor 5 mediates the potentiation of N-methyl-D-aspartate responses in medium spiny striatal neurons.Neuroscience 106, 579–587.

    Article  PubMed  CAS  Google Scholar 

  • Ragnarsson L, M Mortensen, P R Dodd, R J Lewis (2002) Spermine modulation of the glutamate NMDA receptor is differentially responsive to conotokins in normal and Alzheimer disease human cerebral cortex.J. Neurochem. 81, 765–779.

    Article  PubMed  CAS  Google Scholar 

  • Rauca C, P Henrich-Noack, K Schafer, V Hollt and KG Reymann (1998) (S)-4C3HPG reduces infarct size after focal cerebral ischemia.Neuropharmacology 37, 1649–1652.

    Article  PubMed  CAS  Google Scholar 

  • Riedel G, W Wetzel and KG Reymann (1994) (R,S)-β-methyl-4- carboxyphenylglycine (MCPG) blocks spatial learning in rats and long-term potentiation in the dentate gyrusin vivo. Neurosci. Lett. 167, 141–144.

    Article  CAS  Google Scholar 

  • Roche KW, JC Tu, RS Petralia, B Xiao, RJ Wenthold and PF Worley (1999) Homer 1b regulates the trafficking of group I metabotropic glutamate receptors.J. Biol. Chem. 274, 25953- 25957.

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez-Moreno A, A Sistiaga, J Lerma and J Sanchez-Prieto (1998) Switch from facilitation to inhibition of excitatory synaptic transmission by group I mGluR desensitization.Neuron 21, 1477–1486.

    Article  PubMed  CAS  Google Scholar 

  • Rogers J, NR Cooper, S Webster, J Schultz, PL McGeer, SD Styren, WH Civin, L Brachova, B Bradt, P Ward,et al. (1992) Complement activation by β-amyloid in Alzheimer disease.Proc. Natl. Acad. Sci. USA 89, 10016–10020.

    Article  PubMed  CAS  Google Scholar 

  • Rothman SM and JW Olney (1995) Excitotoxicity and the NMDA receptor - still lethal after eight years.Trends Neurosci. 18, 57- 58.

    Article  PubMed  CAS  Google Scholar 

  • Rouse ST, MJ Marino, SR Bradley, H Awad, M Wittmann and PJ Conn (2000) Distribution and roles of metabotropic glutamate receptors in the basal ganglia motor circuit: implications for treatment of Parkinson’s disease and related disorders.Pharmacol. Ther. 88, 427–435.

    Article  PubMed  CAS  Google Scholar 

  • Sacaan AI, FP Bymaster and DD Schoepp (1992) Metabotropic glutamate receptor activation produces extrapyramidal motor system activation that is mediated by striatal dopamine.J. Neurochem. 59, 245–251.

    Article  PubMed  CAS  Google Scholar 

  • Sacaan AI and DD Schoepp (1992) Activation of hippocampal metabotropic excitatory amino acid receptors leads to seizures and neuronal damage.Neurosci. Lett. 139, 77–82

    Article  PubMed  CAS  Google Scholar 

  • Sacaan AI, EM Santori and TS Rao (1998) (S)-4-carboxy-3- hydroxyphenylglycine activates phosphatidyl inositol linked metabotropic glutamate receptors in different brain regions of the neonatal rat.Neurochem. Int. 32, 77–85.

    Article  PubMed  CAS  Google Scholar 

  • Schoepp DD, DE Jane and JA Monn (1999) Pharmacological agents acting at subtypes of metabotropic glutamate receptors.Neuropharmacology 38, 1431–1476.

    Article  PubMed  CAS  Google Scholar 

  • Selkoe DJ (1994) Amyloid β-protein precursor: new clues to the genesis of Alzheimer’s disease.Curr. Opin. Neurobiol. 4, 708- 716.

    Article  PubMed  CAS  Google Scholar 

  • Shigemoto R, T Abe, S Nomura, S Nakanishi and T Hirano (1994) Antibodies inactivating mGluR1 metabotropic glutamate receptor block long-term depression in cultured Purkinje cells.Neuron 12, 1245–1255.

    Article  PubMed  CAS  Google Scholar 

  • Shigemoto R, A Kinoshita, E Wada, S Nomura, H Ohishi, M Takada, PJ Flor, A Neki, T Abe, S Nakanishi and N Mizuno (1997) Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus.J. Neurosci. 17, 7503–7522.

    PubMed  CAS  Google Scholar 

  • Sistiaga A and J Sanchez-Prieto (2000) Protein phosphatase 2B inhibitors mimic the action of arachidonic acid and prolong the facilitation of glutamate release by group I mGlu receptors.Neuropharmacology 39, 1544–1553.

    Article  PubMed  CAS  Google Scholar 

  • Skolnick P, K Boje, R Miller, M Pennington and ML Maccecchini (1992) Noncompetitive inhibition of N-methyl-D-aspartate by conantokin-G: evidence for an allosteric interaction at polyamine sites.J. Neurochem. 59, 1516–1521.

    Article  PubMed  CAS  Google Scholar 

  • Slack BE, RM Nitsch, E Livneh, GM Kunz, Jr, J Breu, H Eldar and RJ Wurtman (1993) Regulation by phorbol esters of amyloid precursor protein release from Swiss 3T3 fibroblasts overexpressing protein kinase Ca.J. Biol. Chem. 268, 21097–21101.

    PubMed  CAS  Google Scholar 

  • Smith-Swintosky VL, LC Pettigrew, SD Craddock, AR Culwell, RE Rydel and MP Mattson (1994) Secreted forms of β-amyloid precursor protein protect against ischemic brain injury.J. Neurochem. 63, 781–784.

    Article  PubMed  CAS  Google Scholar 

  • Spillson AB and JW Russell (2003) Metabotropic glutamate recep- tor regulation of neuronal cell death.Exp. Neurol. 184 Suppl. 1, S97–105.

    Article  PubMed  CAS  Google Scholar 

  • Spooren W, T Ballard, F Gasparini, M Amalric, V Mutel and R Schreiber (2003) Insight into the function of Group I and Group II metabotropic glutamate (mGlu) receptors: behavioural characterization and implications for the treatment of CNS disorders.Behav. Pharmacol. 14, 257–277.

    PubMed  CAS  Google Scholar 

  • Takahashi K, K Tsuchida, Y Tanabe, M Masu and S Nakanishi (1993) Role of the large extracellular domain of metabotropic glutamate receptors in agonist selectivity determination.J. Biol. Chem. 268, 19341–19345.

    PubMed  CAS  Google Scholar 

  • Tanabe Y, A Nomura, M Masu, R Shigemoto, N Mizuno and S Nakanishi (1993) Signal transduction, pharmacological properties, and expression patterns of two rat metabotropic glutamate receptors, mGluR3 andmGluR4.J. Neurosci. 13, 1372–1378.

    PubMed  CAS  Google Scholar 

  • Tanaka J, S Nakagawa, E Kushiya, M Yamasaki, M Fukaya, T Iwanaga, MI Simon, K Sakimura, M Kano and M Watanabe (2000) Gq protein a subunits Gaq and Ga1 1 are localized at post- synaptic extra-junctional membrane of cerebellar Purkinje cells and hippocampal pyramidal cells.Eur. J. Neurosci. 12, 781–792.

    Article  PubMed  CAS  Google Scholar 

  • Thomsen C and NO Dalby (1998) Roles of metabotropic glutamate receptor subtypes in modulation of pentylenetetrazole-induced seizure activity in mice.Neuropharmacology 37, 1465–1473.

    Article  PubMed  CAS  Google Scholar 

  • Tones MA, N Bendali, PJ Flor, T Knopfel and R Kuhn (1995) The agonist selectivity of a class III metabotropic glutamate receptor, human mGluR4a, is determined by the N-terminal extracellular domain.Neuroreport 7, 117–120.

    PubMed  CAS  Google Scholar 

  • Tu JC, B Xiao, JP Yuan, AA Lanahan, K Leoffert, M Li, DJ Linden and PF Worley (1998) Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors.Neuron 21, 717–726.

    Article  PubMed  CAS  Google Scholar 

  • Tu JC, B Xiao, S Naisbitt, JP Yuan, RS Petralia, P Brakeman, A Doan, VK Aakalu, AA Lanahan, M Sheng and PF Worley (1999) Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins.Neuron 23, 583–592.

    Article  PubMed  CAS  Google Scholar 

  • Ugolini A, M Corsi and F Bordi (1997) Potentiation of NMDA and AMPA responses by group I mGluR in spinal cord motoneurons.Neuropharmacology 36, 1047–1055.

    Article  PubMed  CAS  Google Scholar 

  • Ugolini A, M Corsi and F Bordi (1999) Potentiation of NMDA and AMPA responses by the specific mGluR5 agonist CHPG in spinal cord motoneurons.Neuropharmacology 38, 1569–1576.

    Article  PubMed  CAS  Google Scholar 

  • Ulus IH and RJ Wurtman (1997) Metabotropic glutamate receptor agonists increase release of soluble amyloid precursor protein derivatives from rat brain cortical and hippocampal slices.J. Pharmacol. Exp. Ther. 281, 149–154.

    PubMed  CAS  Google Scholar 

  • Varney MA, ND Cosford, C Jachec, SP Rao, A Sacaan, FF Lin, L Bleicher, EM Santori, PJ Flor, H Allgeier, F Gasparini, R Kuhn, SD Hess, G Velicelebi and EC Johnson (1999) SIB-1757 and SIB- 1893: selective, noncompetitive antagonists of metabotropic glutamate receptor type 5.J. Pharmacol. Exp. Ther. 290, 170–181.

    PubMed  CAS  Google Scholar 

  • Vazquez E, I Herrero, MT Miras-Portugal and J Sanchez-Prieto (1994) Role of arachidonic acid in the facilitation of glutamate release from rat cerebrocortical synaptosomes independent of metabotropic glutamate receptor responses.Neurosci. Lett. 174, 9–13.

    Article  PubMed  CAS  Google Scholar 

  • Vidnyanszky Z, J Hamori, L Negyessy, D Ruegg, T Knopfel, R Kuhn and TJ Gorcs (1994) Cellular and subcellular localization of the mGluR5a metabotropic glutamate receptor in rat spinal cord.Neuroreport 6, 209–213.

    Article  PubMed  CAS  Google Scholar 

  • Vidnyanszky Z, TJ Gorcs, L Negyessy, Z Borostyankio, T Knopfel and J Hamori (1996) Immunocytochemical visualization of the mGluR1a metabotropic glutamate receptor at synapses of corti- cothalamic terminals originating from area 17 of the rat.Eur. J. Neurosci. 8, 1061–1071.

    Article  PubMed  CAS  Google Scholar 

  • Webster S, LF Lue, L Brachova, AJ Tenner, PL McGeer, K Terai, DG Walker, B Bradt, NR Cooper and J Rogers (1997) Molecular and cellular characterization of the membrane attack complex, C5b-9, in Alzheimer’s disease.Neurobiol. Aging 18, 415–421.

    Article  PubMed  CAS  Google Scholar 

  • Weidemann A, G Konig, D Bunke, P Fischer, JM Salbaum, CL Masters and K Beyreuther (1989) Identification, biogenesis, and localization of precursors of Alzheimer’s disease A4 amyloid protein.Cell 57, 115–126.

    Article  PubMed  CAS  Google Scholar 

  • Winder DG and PJ Conn (1996) Roles of metabotropic glutamate receptors in glial function and glial-neuronal communication.J. Neurosci. Res. 46, 131–137.

    Article  PubMed  CAS  Google Scholar 

  • Xiao B, JC Tu, RS Petralia, JP Yuan, A Doan, CD Breder, A Ruggiero, AA Lanahan, RJ Wenthold and PF Worley (1998) Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins.Neuron 21, 707–716.

    Article  PubMed  CAS  Google Scholar 

  • Yu SP, SL Sensi, LM Canzoniero, A Buisson and DW Choi (1997) Membrane-delimited modulation of NMDA currents by metabotropic glutamate receptor subtypes 1/5 in cultured mouse cortical neurons.J. Physiol. 499, 721–732.

    PubMed  CAS  Google Scholar 

  • Zheng H, M Jiang, ME Trumbauer, DJ Sirinathsinghji, R Hopkins, DW Smith, RP Heavens, GR Dawson, S Boyce, MW Conneret al. (1995) β-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity.Cell 81, 525–531.

    Article  PubMed  CAS  Google Scholar 

  • Zhou LM, GI Szendrei, LH Fossom, ML Maccecchini, P Skolnick and L Otvos Jr (1996) Synthetic analogues of conantokin-G: NMDA antagonists acting through a novel polyamine-coupled site.J. Neurochem. 66, 620–628.

    Article  PubMed  CAS  Google Scholar 

  • Zucker RS (1999) Calcium- and activity-dependent synaptic plasticity.Curr. Opin. Neurobiol. 9, 305–313.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. School of Molecular and Microbial Sciences, University of Queensland, 4072, Brisbane, Australia

    Vicky W. -W. Tsai, Heather L. Scott & Peter R. Dodd

  2. Institute for Molecular Bioscience, University of Queensland, 4072, Brisbane, Australia

    Richard J. Lewis

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  1. Vicky W. -W. Tsai
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  2. Heather L. Scott
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  3. Richard J. Lewis
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  4. Peter R. Dodd
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Correspondence to Peter R. Dodd.

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Tsai, V.W.W., Scott, H.L., Lewis, R.J. et al. The role of group I metabotropic glutamate receptors in neuronal excitotoxicity in alzheimer’s disease. neurotox res 7, 125–141 (2005). https://doi.org/10.1007/BF03033782

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