AZD1080, a novel GSK3 inhibitor, rescues synaptic plasticity deficits in rodent brain and exhibits peripheral target engagement in humans

Journal of Neurochemistry

Volumn 125, Issue 3, 2013, Pages 446-456

  Georgievska, Biljana ^a   Sandin, Johan ^a   Doherty, James ^a   Mörtberg, Anette ^a   Neelissen, Jan ^a   Andersson, Anita ^a   Gruber, Susanne ^a   Nilsson, Yvonne ^a   Schött, Pär ^a   Arvidsson, Per I ^a   Hellberg, Sven ^a   Osswald, Gunilla ^a   Berg, Stefan ^a   Fälting, Johanna ^a   Bhat, Ratan V ^a  

^a ASTRAZENECA R AND D   (Sweden)

Author keywords

Alzheimer's disease; cognition; glycogen synthase kinase 3; tau

Indexed keywords

2 HYDROXY 3 [5 [(MORPHOLIN 4 YL)METHYL]PYRIDIN 2 YL] 1H INDOLE 5 CARBONITRILE CITRATE; AZD 1080; GLYCOGEN SYNTHASE; GLYCOGEN SYNTHASE KINASE 3 INHIBITOR; GLYCOGEN SYNTHASE KINASE 3BETA; PLACEBO; TAU PROTEIN; UNCLASSIFIED DRUG;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BRAIN SLICE; CELL STRAIN 3T3; COGNITION; CONDITIONING; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG HALF LIFE; DRUG SELECTIVITY; FEMALE; HIPPOCAMPUS; HUMAN; HUMAN EXPERIMENT; IN VITRO STUDY; IN VIVO STUDY; LONG TERM POTENTIATION; MALE; MOUSE; NERVE CELL PLASTICITY; NEUROLOGIC EXAMINATION; NONHUMAN; NORMAL HUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; PHARMACODYNAMICS; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RANDOMIZED CONTROLLED TRIAL; RAT; SIGNAL TRANSDUCTION;

ANIMALS; CELL LINE, TRANSFORMED; COGNITION DISORDERS; CRYSTALLOGRAPHY; DISEASE MODELS, ANIMAL; DIZOCILPINE MALEATE; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; ELECTRIC STIMULATION; ENZYME INHIBITORS; EXCITATORY AMINO ACID ANTAGONISTS; EXCITATORY POSTSYNAPTIC POTENTIALS; GLYCOGEN SYNTHASE; GLYCOGEN SYNTHASE KINASE 3; HIPPOCAMPUS; HUMANS; INDOLES; LEUKOCYTES, MONONUCLEAR; LONG-TERM POTENTIATION; MALE; MICE; MIDDLE AGED; PHOSPHORYLATION; PROTEIN BINDING; PROTEIN KINASES; PYRIDINES; RATS; RATS, SPRAGUE-DAWLEY; TAU PROTEINS;

MUS; RATTUS; RODENTIA;

EID: 84876666322     PISSN: 00223042     EISSN: 14714159     Source Type: Journal    
DOI: 10.1111/jnc.12203     Document Type: Article

References (33)

1. Alzheimer's Association (2011) Alzheimer's Association Report Alzheimer's disease facts and figures. Alzheimers Dement. 7, 208-244.
2. Ballatore C., Lee V. M., and, Trojanowski J. Q., (2007) Tau-mediated neurodegeneration in Alzheimer's disease and related disorders. Nat. Rev. Neurosci. 8, 663-672.
3. Bardgett M. E., Boeckman R., Krochmal D., Fernando H., Ahrens R., and, Csernansky J. G., (2003) NMDA receptor blockade and hippocampal neuronal loss impair fear conditioning and position habit reversal in C57Bl/6 mice. Brain Res. Bull. 60, 131-142.
4. Berg S., Bergh M., Hellberg S., et al,. (2012) Discovery of Novel Potent and Highly Selective Glycogen Synthase Kinase-3β (GSK3β) Inhibitors for Alzheimer's Disease: Design, Synthesis, and Characterization of Pyrazines. J. Med. Chem. 55, 9107-9119.
5. Bhat R. V., and, Budd S. L., (2002) GSK3beta signaling: casting a wide net in Alzheimer's disease. Neurosignals 11, 251-261.
6. Bhat R., Xue Y., Berg S., et al,. (2003) Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. J. Biol. Chem. 278, 45937-45945.
7. Bhat R. V., Budd Haeberlein S. L., and, Avila J., (2004) Glycogen synthase kinase 3: a drug target for CNS therapies. J. Neurochem. 89, 1313-1317.
8. Citri A., and, Malenka R. C., (2008) Synaptic plasticity: multiple forms, functions, and mechanisms. Neuropsychopharmacology 33, 18-41.
9. Coan E. J., Saywood W., and, Collingridge G. L., (1997) MK-801 blocks NMDA receptor mediated synaptic transmission and long term potentiation in rat hippocampal slices. Neurosci. Lett. 80, 111-114.
10. Davies S. P., Reddy H., Caivano M., and, Cohen P., (2000) Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem. J. 351, 95-105.
11. Frankiewicz T., Potier B., Bashir Z. I., Collingridge G. L., and, Parsons C. G., (1996) Effects of memantine and MK-801 on NMDA-induced currents in cultured neurons and on synaptic transmission and LTP in area CA1 of rat hippocampal slices. Br. J. Pharmacol. 117, 689-697.
12. Hanger D. P., Hughes K., Woodgett J. R., Brion J. P., and, Anderton B. H., (1992) Glycogen synthase kinase-3 induces Alzheimer's disease-like phosphorylation of tau: generation of paired helical filament epitopes and neuronal localisation of the kinase. Neurosci. Lett. 147, 58-62.
13. Hernández F., Borrell J., Guaza C., Avila J., and, Lucas J. J., (2002) Spatial learning deficit in transgenic mice that conditionally over-express GSK-3beta in the brain but do not form tau filaments. J. Neurochem. 83, 1529-1533.
14. Hooper C., Markevich V., Plattner F., et al,. (2007) Glycogen synthase kinase-3 inhibition is integral to long-term potentiation. Eur. J. Neurosci. 25, 81-86.
15. Hooper C., Killick R., and, Lovestone S., (2008) The GSK3 hypothesis of Alzheimer's disease. J. Neurochem. 104, 1433-1439.
16. Imahori K., and, Uchida T., (1997) Physiology and pathology of tau protein kinases in relation to Alzheimer's disease. J. Biochem. 121, 179-188.
17. Ishiguro K., Shiratsuchi A., Sato S., Omori A., Arioka M., Kobayashi S., Uchida T., and, Imahori K., (1993) Glycogen synthase kinase 3 beta is identical to tau protein kinase I generating several epitopes of paired helical filaments. FEBS Lett. 325, 167-172.
18. Jo J., Whitcomb D. J., Olsen K. M., et al,. (2011) Aβ(1-42) inhibition of LTP is mediated by a signaling pathway involving caspase-3, Akt1 and GSK-3β. Nat. Neurosci. 14 (5), 545-547.
19. Kemp J. A., Fisher A. C., and, Wong E. H. F., (1987) Non-competitive antagonists of excitatory amino acid receptors. Trends Neurosci. 10, 294-298.
20. Kremer A., Louis J. V., Jaworski T., and, Van Leuven F., (2011) GSK3 and Alzheimer's Disease: Facts and Fiction. Front. Mol. Neurosci. 4, 1-10.
21. Li X., Friedman A. B., Zhu W., Wang L., Boswell S., May R. S., Davis L. L., and, Jope R. S., (2007) Lithium regulates glycogen synthase kinase-3beta in human peripheral blood mononuclear cells: implication in the treatment of bipolar disorder. Biol. Psychiatry 61, 216-222.
22. Lovestone S., Reynolds C. H., Latimer D., et al,. (1994) Alzheimer's disease-like phosphorylation of the microtubule-associated protein tau by glycogen synthase kinase-3 in transfected mammalian cells. Curr. Biol. 4, 1077-1086.
23. Lucas J. J., Hernández F., Gõmez-Ramos P., Morán M. A., Hen R., and, Avila J., (2001) Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice. EMBO J. 20, 27-39.
24. Onishi T., Iwashita H., Uno Y., Kunimoto J., Saitoh M., Kimura E., Fujita H., Uchiyama N., Kori M., and, Takizawa M., (2011) A novel glycogen synthase kinase-3 inhibitor 2-methyl-5-(3-{4-[(S )-methylsulfinyl] phenyl}-1-benzofuran-5-yl)-1,3,4-oxadiazole decreases tau phosphorylation and ameliorates cognitive deficits in a transgenic model of Alzheimer's disease. J. Neurochem. 119, 1330-1340.
25. Pei J. J., Braak E., Braak H., Grundke-Iqbal I., Iqbal K., Winblad B., and, Cowburn R. F., (1999) Distribution of active glycogen synthase kinase 3beta (GSK-3beta) in brains staged for Alzheimer disease neurofibrillary changes. J. Neuropathol. Exp. Neurol. 58, 1010-1019.
26. Peineau S., Taghibiglou C., Bradley C., et al,. (2007) LTP inhibits LTD in the hippocampus via regulation of GSK3β. Neuron 53, 703-717.
27. Peineau S., Bradley C., Taghibiglou C., Doherty A., Bortolotto Z. A., Wang Y. T., and, Collingridge G. L., (2008) The role of GSK-3 in synaptic plasticity. Br. J. Pharmacol. 153, S428-S437.
28. Peineau S., Nicolas C. S., Bortolotto Z. A., Bhat R. V., Ryves W. J., Harwood A. J., Dournaud P., Fitzjohn S. M., and, Collingridge G. L., (2009) A systematic investigation of the protein kinases involved in NMDA receptor-dependent LTD: evidence for a role of GSK-3 but not other serine/threonine kinases. Mol. Brain 2, 22.
29. Querfurth H. W., and, LaFerla F. M., (2010) Alzheimer's disease. N. Engl. J. Med. 362, 329-344.
30. Takahashi M., Tomizawa K., Kato R., Sato K., Uchida T., Fujita S. C., and, Imahori K., (1994) Localization and developmental changes of τ protein kinase I/glycogen synthase kinase-3β in rat brain. J. Neurochem. 63, 245-255.
31. Takahashi H., Tomizawa K., and, Ishiguro K., (2000) Distribution of tau protein kinase I/glycogen synthase kinase-3beta, phosphatases 2A and 2B, and phosphorylated tau in the developing rat brain. Brain Res. 857, 193-206.
32. Woodgett J. R., (1991) cDNA cloning and properties of glycogen synthase kinase-3. Methods Enzymol. 200, 564-577.
33. Yamaguchi H., Ishiguro K., Uchida T., Takashima A., Lemere C. A., and, Imahori K., (1996) Preferential labeling of Alzheimer neurofibrillary tangles with antisera for tau protein kinase (TPK) I/glycogen synthase kinase-3 beta and cyclin-dependent kinase 5, a component of TPK II. Acta Neuropathol. 92, 232-241.