Metabotropic glutamate receptor 5 positive allosteric modulators are neuroprotective in a mouse model of Huntington's disease

British Journal of Pharmacology

Volumn 169, Issue 4, 2013, Pages 909-921

  Doria, J G ^a   Silva, F R ^a   De Souza, J M ^a   Vieira, L B ^a   Carvalho, T G ^a   Reis, H J ^a   Pereira, G S ^a   Dobransky, T ^b   Ribeiro, F M ^a  

^a FEDERAL UNIVERSITY OF MINAS GERAIS   (Brazil)

^b DB Biotech   (Slovakia)

Author keywords

AKT; calcium; cell death; cell signalling; glutamate; Huntington's disease; mGluR5

Indexed keywords

3 CYANO N (1,3 DIPHENYL 1H PYRAZOL 5 YL)BENZAMIDE; [(3 FLUOROPHENYL)METHYLENE]HYDRAZONE 3 FLUOROBENZALDEHYDE; CALCIUM ION; GLUTAMIC ACID; METABOTROPIC GLUTAMATE RECEPTOR 5 ALLOSTERIC MODULATOR; N [1 (2 FLUOROPHENYL) 3 PHENYL 1H PYRAZOL 5 YL] 4 NITROBENZAMIDE; N METHYL DEXTRO ASPARTIC ACID; NEUROPROTECTIVE AGENT; PROTEIN KINASE B; UNCLASSIFIED DRUG; VU 1545;

AMNESIA; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN NERVE CELL; CALCIUM CELL LEVEL; CALCIUM TRANSPORT; CELL PROTECTION; CONCENTRATION RESPONSE; CONTROLLED STUDY; CORPUS STRIATUM; EMBRYO; ENZYME ACTIVATION; ENZYME INHIBITION; HUNTINGTON CHOREA; MOLECULAR MECHANICS; MOUSE; NERVE CELL NECROSIS; NEUROPROTECTION; NONHUMAN; PRIORITY JOURNAL; RECOGNITION; TASK PERFORMANCE; WESTERN BLOTTING;

ALLOSTERIC REGULATION; ANIMALS; BEHAVIOR, ANIMAL; CELL DEATH; CELLS, CULTURED; CORPUS STRIATUM; EMBRYO, MAMMALIAN; ENZYME ACTIVATION; HUNTINGTON DISEASE; MEMORY DISORDERS; MICE; MICE, INBRED STRAINS; MICE, TRANSGENIC; NERVE TISSUE PROTEINS; NEURONS; NEUROPROTECTIVE AGENTS; NOOTROPIC AGENTS; NUCLEAR PROTEINS; PHOSPHORYLATION; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTO-ONCOGENE PROTEINS C-AKT; RECEPTOR, METABOTROPIC GLUTAMATE 5;

EID: 84878278670     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.12164     Document Type: Article

References (44)

1. Awad H, Hubert GW, Smith Y, Levey AI, Conn PJ, (2000). Activation of metabotropic glutamate receptor 5 has direct excitatory effects and potentiates NMDA receptor currents in neurons of the subthalamic nucleus. J Neurosci 20: 7871-7879.
2. Bagetta V, Ghiglieri V, Sgobio C, Calabresi P, Picconi B, (2010). Synaptic dysfunction in Parkinson's disease. Biochem Soc Trans 38: 493-497.
3. Baskys A, Bayazitov I, Fang L, Blaabjerg M, Poulsen FR, Zimmer J, (2005). Group I metabotropic glutamate receptors reduce excitotoxic injury and may facilitate neurogenesis. Neuropharmacology 49 (Suppl. 1): 146-156.
4. Bradley SJ, Watson JM, Challiss RA, (2009). Effects of positive allosteric modulators on single-cell oscillatory Ca2+ signaling initiated by the type 5 metabotropic glutamate receptor. Mol Pharmacol 76: 1302-1313.
5. Bruno V, Battaglia G, Copani A, Cespedes VM, Galindo MF, Cena V, et al. (2001). An activity-dependent switch from facilitation to inhibition in the control of excitotoxicity by group I metabotropic glutamate receptors. Eur J Neurosci 13: 1469-1478.
6. Calabresi P, Centonze D, Pisani A, Bernardi G, (1999). Metabotropic glutamate receptors and cell-type-specific vulnerability in the striatum: implication for ischemia and Huntington's disease. Exp Neurol 158: 97-108.
7. Chen T, Cao L, Dong W, Luo P, Liu W, Qu Y, et al. (2012). Protective effects of mGluR5 positive modulators against traumatic neuronal injury through PKC-dependent activation of MEK/ERK pathway. Neurochem Res 37: 983-990.
8. Conn PJ, Lindsley CW, Jones CK, (2009). Activation of metabotropic glutamate receptors as a novel approach for the treatment of schizophrenia. Trends Pharmacol Sci 30: 25-31.
9. Datta SR, Brunet A, Greenberg ME, (1999). Cellular survival: a play in three Akts. Genes Dev 13: 2905-2927.
10. DiFiglia M, (1990). Excitotoxic injury of the neostriatum: a model for Huntington's disease. Trends Neurosci 13: 286-289.
11. Donev R, Kolev M, Millet B, Thome J, (2009). Neuronal death in Alzheimer's disease and therapeutic opportunities. J Cell Mol Med 13: 4329-4348.
12. Ennaceur A, Delacour J, (1988). A new one-trial test for neurobiological studies of memory in rats. 1: behavioral data. Behav Brain Res 31: 47-59.
13. Gines S, Ivanova E, Seong IS, Saura CA, MacDonald ME, (2003). Enhanced Akt signaling is an early pro-survival response that reflects N-methyl-D-aspartate receptor activation in Huntington's disease knock-in striatal cells. J Biol Chem 278: 50514-50522.
14. Gray LJ, Hannan AJ, Zhang X, (2012). Metabotropic glutamate receptors as targets for novel antipsychotic treatments. Curr Pharm Biotechnol 13: 1522-1534.
15. Gray M, Shirasaki DI, Cepeda C, Andre VM, Wilburn B, Lu XH, et al. (2008). Full-length human mutant huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice. J Neurosci 28: 6182-6195.
16. Group THsDCR (1993). A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72: 971-983.
17. Grynkiewicz G, Poenie M, Tsien RY, (1985). A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260: 3440-3450.
18. Hou L, Klann E, (2004). Activation of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin signaling pathway is required for metabotropic glutamate receptor-dependent long-term depression. J Neurosci 24: 6352-6361.
19. Humbert S, Bryson EA, Cordelieres FP, Connors NC, Datta SR, Finkbeiner S, et al. (2002). The IGF-1/Akt pathway is neuroprotective in Huntington's disease and involves Huntingtin phosphorylation by Akt. Dev Cell 2: 831-837.
20. Kandel ES, Hay N, (1999). The regulation and activities of the multifunctional serine/threonine kinase Akt/PKB. Exp Cell Res 253: 210-229.
21. Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG, (2010). NC3Rs Reporting Guidelines Working Group. Br J Pharmacol 160: 1577-1579.
22. Lazaroni TL, Raslan AC, Fontes WR, de Oliveira ML, Bader M, Alenina N, et al. (2012). Angiotensin-(1-7)/Mas axis integrity is required for the expression of object recognition memory. Neurobiol Learn Mem 97: 113-123.
23. Li SH, Li XJ, (2004). Huntingtin-protein interactions and the pathogenesis of Huntington's disease. Trends Genet 20: 146-154.
24. McGrath J, Drummond G, McLachlan E, Kilkenny C, Wainwright C, (2010). Guidelines for reporting experiments involving animals: the ARRIVE guidelines. Br J Pharmacol 160: 1573-1576.
25. Mao L, Yang L, Tang Q, Samdani S, Zhang G, Wang JQ, (2005). The scaffold protein Homer1b/c links metabotropic glutamate receptor 5 to extracellular signal-regulated protein kinase cascades in neurons. J Neurosci 25: 2741-2752.
26. Nicoletti F, Bruno V, Copani A, Casabona G, Knopfel T, (1996). Metabotropic glutamate receptors: a new target for the therapy of neurodegenerative disorders? Trends Neurosci 19: 267-271.
27. Orrenius S, Zhivotovsky B, Nicotera P, (2003). Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol 4: 552-565.
28. Ribeiro FM, Paquet M, Cregan SP, Ferguson SS, (2010a). Group I metabotropic glutamate receptor signalling and its implication in neurological disease. CNS Neurol Disord Drug Targets 9: 574-595.
29. Ribeiro FM, Paquet M, Ferreira LT, Cregan T, Swan P, Cregan SP, et al. (2010b). Metabotropic glutamate receptor-mediated cell signaling pathways are altered in a mouse model of Huntington's disease. J Neurosci 30: 316-324.
30. Ribeiro FM, Pires RG, Ferguson SS, (2011). Huntington's disease and Group I metabotropic glutamate receptors. Mol Neurobiol 43: 1-11.
31. Ritzen A, Mathiesen JM, Thomsen C, (2005). Molecular pharmacology and therapeutic prospects of metabotropic glutamate receptor allosteric modulators. Basic Clin Pharmacol Toxicol 97: 202-213.
32. Rodriguez AL, Grier MD, Jones CK, Herman EJ, Kane AS, Smith RL, et al. (2010). Discovery of novel allosteric modulators of metabotropic glutamate receptor subtype 5 reveals chemical and functional diversity and in vivo activity in rat behavioral models of anxiolytic and antipsychotic activity. Mol Pharmacol 78: 1105-1123.
33. Rong R, Ahn JY, Huang H, Nagata E, Kalman D, Kapp JA, et al. (2003). PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase, preventing neuronal apoptosis. Nat Neurosci 6: 1153-1161.
34. Schiefer J, Sprunken A, Puls C, Luesse HG, Milkereit A, Milkereit E, et al. (2004). The metabotropic glutamate receptor 5 antagonist MPEP and the mGluR2 agonist LY379268 modify disease progression in a transgenic mouse model of Huntington's disease. Brain Res 1019: 246-254.
35. Southwell AL, Ko J, Patterson PH, (2009). Intrabody gene therapy ameliorates motor, cognitive, and neuropathological symptoms in multiple mouse models of Huntington's disease. J Neurosci 29: 13589-13602.
36. Spear N, Gadient RA, Wilkins DE, Do M, Smith JS, Zeller KL, et al. (2011). Preclinical profile of a novel metabotropic glutamate receptor 5 positive allosteric modulator. Eur J Pharmacol 659: 146-154.
37. Tang TS, Tu H, Chan EY, Maximov A, Wang Z, Wellington CL, et al. (2003). Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1. Neuron 39: 227-239.
38. Tang TS, Slow E, Lupu V, Stavrovskaya IG, Sugimori M, Llinas R, et al. (2005). Disturbed Ca2+ signaling and apoptosis of medium spiny neurons in Huntington's disease. Proc Natl Acad Sci U S A 102: 2602-2607.
39. Vonsattel JP, DiFiglia M, (1998). Huntington disease. J Neuropathol Exp Neurol 57: 369-384.
40. Warby SC, Doty CN, Graham RK, Shively J, Singaraja RR, Hayden MR, (2009). Phosphorylation of huntingtin reduces the accumulation of its nuclear fragments. Mol Cell Neurosci 40: 121-127.
41. Young AB, (2003). Huntingtin in health and disease. J Clin Invest 111: 299-302.
42. Zeron MM, Chen N, Moshaver A, Lee AT, Wellington CL, Hayden MR, et al. (2001). Mutant huntingtin enhances excitotoxic cell death. Mol Cell Neurosci 17: 41-53.
43. Zeron MM, Hansson O, Chen N, Wellington CL, Leavitt BR, Brundin P, et al. (2002). Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington's disease. Neuron 33: 849-860.
44. Zhang Y, Rodriguez AL, Conn PJ, (2005). Allosteric potentiators of metabotropic glutamate receptor subtype 5 have differential effects on different signaling pathways in cortical astrocytes. J Pharmacol Exp Ther 315: 1212-1219.