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International Journal of Alzheimer’s Disease
Volume 2011 (2011), Article ID 189246, 9 pages
http://dx.doi.org/10.4061/2011/189246
Review Article

GSK-3 in Neurodegenerative Diseases

1Mental Health Research Institute, 155 Oak Street, Parkville, VIC 3052, Australia
2Department of Pathology, The University of Melbourne, Carlton, VIC 3010, Australia
3Center for Neuroscience, The University of Melbourne, Carlton, VIC 3010, Australia

Received 27 January 2011; Accepted 7 March 2011

Academic Editor: Peter Crouch

Copyright © 2011 Peng Lei et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. N. Embi, D. B. Rylatt, and P. Cohen, “Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase,” European Journal of Biochemistry, vol. 107, no. 2, pp. 519–527, 1980. View at Google Scholar · View at Scopus
  2. D. B. Rylatt, A. Aitken, T. Bilham, G. D. Condon, N. Embi, and P. Cohen, “Glycogen synthase from rabbit skeletal muscle. Amino acid sequence at the sites phosphorylated by glycogen synthase kinase-3, and extension of the N-terminal sequence containing the site phosphorylated by phosphorylase kinase,” European Journal of Biochemistry, vol. 107, no. 2, pp. 529–537, 1980. View at Google Scholar · View at Scopus
  3. L. Kockeritz, B. Doble, S. Patel, and J. R. Woodgett, “Glycogen synthase kinase-3—an overview of an over-achieving protein kinase,” Current Drug Targets, vol. 7, no. 11, pp. 1377–1388, 2006. View at Google Scholar · View at Scopus
  4. S. Frame and P. Cohen, “GSK3 takes centre stage more than 20 years after its discovery,” Biochemical Journal, vol. 359, no. 1, pp. 1–16, 2001. View at Publisher · View at Google Scholar · View at Scopus
  5. J. R. Woodgett, “Molecular cloning and expression of glycogen synthase kinase-3/factor A,” The EMBO Journal, vol. 9, no. 8, pp. 2431–2438, 1990. View at Google Scholar · View at Scopus
  6. H. B. Yao, P. C. Shaw, C. C. Wong, and D. C. C. Wan, “Expression of glycogen synthase kinase-3 isoforms in mouse tissues and their transcription in the brain,” Journal of Chemical Neuroanatomy, vol. 23, no. 4, pp. 291–297, 2002. View at Publisher · View at Google Scholar · View at Scopus
  7. K. F. Lau, C. C. J. Miller, B. H. Anderton, and P. C. Shaw, “Expression analysis of glycogen synthase kinase-3 in human tissues,” Journal of Peptide Research, vol. 54, no. 1, pp. 85–91, 1999. View at Publisher · View at Google Scholar · View at Scopus
  8. M. Aoki, M. Iwamoto-Sugai, I. Sugiura et al., “Expression, purification and crystallization of human tau-protein kinase I/glycogen synthase kinase-3β,” Acta Crystallographica Section D, vol. 56, no. 11, pp. 1464–1465, 2000. View at Publisher · View at Google Scholar · View at Scopus
  9. R. Dajani, E. Fraser, S. M. Roe et al., “Crystal structure of glycogen synthase kinase 3β: structural basis for phosphate-primed substrate specificity and autoinhibition,” Cell, vol. 105, no. 6, pp. 721–732, 2001. View at Publisher · View at Google Scholar · View at Scopus
  10. M. P. M. Soutar, W.-Y. Kim, R. Williamson et al., “Evidence that glycogen synthase kinase-3 isoforms have distinct substrate preference in the brain,” Journal of Neurochemistry, vol. 115, no. 4, pp. 974–983, 2010. View at Publisher · View at Google Scholar
  11. A. Cole, S. Frame, and P. Cohen, “Further evidence that the tyrosine phosphorylation of glycogen synthase kinase-3 (GSK3) in mammalian cells is an autophosphorylation event,” Biochemical Journal, vol. 377, no. 1, pp. 249–255, 2004. View at Publisher · View at Google Scholar · View at Scopus
  12. D. A. E. Cross, D. R. Alessi, P. Cohen, M. Andjelkovich, and B. A. Hemmings, “Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B,” Nature, vol. 378, no. 6559, pp. 785–789, 1995. View at Publisher · View at Google Scholar · View at Scopus
  13. M. Lesort, R. S. Jope, and G. V. W. Johnson, “Insulin transiently increases tau phosphorylation: involvement of glycogen synthase kinase-3β and Fyn tyrosine kinase,” Journal of Neurochemistry, vol. 72, no. 2, pp. 576–584, 1999. View at Publisher · View at Google Scholar · View at Scopus
  14. S. J. Liu, AI. H. Zhang, H. L. Li et al., “Overactivation of glycogen synthase kinase-3 by inhibition of phosphoinositol-3 kinase and protein kinase C leads to hyperphosphorylation of tau and impairment of spatial memory,” Journal of Neurochemistry, vol. 87, no. 6, pp. 1333–1344, 2003. View at Google Scholar · View at Scopus
  15. V. Meske, F. Albert, and T. G. Ohm, “Coupling of mammalian target of rapamycin with phosphoinositide 3-kinase signaling pathway regulates protein phosphatase 2a- and glycogen synthase kinase-3β-dependent phosphorylation of tau,” Journal of Biological Chemistry, vol. 283, no. 1, pp. 100–109, 2008. View at Publisher · View at Google Scholar · View at Scopus
  16. T. Isagawa, H. Mukai, K. Oishi et al., “Dual effects of PKNα and protein kinase C on phosphorylation of tau protein by glycogen synthase kinase-3β,” Biochemical and Biophysical Research Communications, vol. 273, no. 1, pp. 209–212, 2000. View at Publisher · View at Google Scholar · View at Scopus
  17. I. Tsujio, T. Tanaka, T. Kudo et al., “Inactivation of glycogen synthase kinase-3 by protein kinase C δ: implications for regulation of τ phosphorylation,” FEBS Letters, vol. 469, no. 1, pp. 111–117, 2000. View at Publisher · View at Google Scholar · View at Scopus
  18. T. M. Thornton, G. Pedraza-Alva, B. Deng et al., “Phosphorylation by p38 MAPK as an alternative pathway for GSK-3β inactivation,” Science, vol. 320, no. 5876, pp. 667–670, 2008. View at Publisher · View at Google Scholar · View at Scopus
  19. F. Hernández, E. Langa, R. Cuadros, J. Avila, and N. Villanueva, “Regulation of GSK3 isoforms by phosphatases PP1 and PP2A,” Molecular and Cellular Biochemistry, vol. 344, no. 1-2, pp. 211–215, 2010. View at Publisher · View at Google Scholar
  20. S. Peineau, C. Taghibiglou, C. Bradley et al., “LTP inhibits LTD in the hippocampus via regulation of GSK-3β,” Neuron, vol. 53, no. 5, pp. 703–717, 2007. View at Publisher · View at Google Scholar · View at Scopus
  21. Y. Kim, Y. I. Lee, M. Seo et al., “Calcineurin dephosphorylates glycogen synthase kinase-3 beta at serine-9 in neuroblast-derived cells,” Journal of Neurochemistry, vol. 111, no. 2, pp. 344–354, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. G. P. Liu, Y. Zhang, X. Q. Yao et al., “Activation of glycogen synthase kinase-3 inhibits protein phosphatase-2A and the underlying mechanisms,” Neurobiology of Aging, vol. 29, no. 9, pp. 1348–1358, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. K. Blennow, M. J. de Leon, and H. Zetterberg, “Alzheimer's disease,” The Lancet, vol. 368, no. 9533, pp. 387–403, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. C. L. Masters, G. Simms, and N. A. Weinman, “Amyloid plaque core protein in Alzheimer disease and Down syndrome,” Proceedings of the National Academy of Sciences of the United States of America, vol. 82, no. 12, pp. 4245–4249, 1985. View at Google Scholar · View at Scopus
  25. C. Haass, M. G. Schlossmacher, A. Y. Hung et al., “Amyloid β-peptide is produced by cultured cells during normal metabolism,” Nature, vol. 359, no. 6393, pp. 322–325, 1992. View at Publisher · View at Google Scholar · View at Scopus
  26. R. E. Tanzi, “The Alzheimer disease-associated amyloid beta protein precursor gene and familial Alzheimer disease,” Progress in Clinical and Biological Research, vol. 360, pp. 187–199, 1990. View at Google Scholar · View at Scopus
  27. R. Vassar, B. D. Bennett, S. Babu-Khan et al., “β-Secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE,” Science, vol. 286, no. 5440, pp. 735–741, 1999. View at Publisher · View at Google Scholar · View at Scopus
  28. M. S. Wolfe, W. Xia, B. L. Ostaszewski, T. S. Diehl, W. T. Kimberly, and D. J. Selkoe, “Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity,” Nature, vol. 398, no. 6727, pp. 513–517, 1999. View at Publisher · View at Google Scholar · View at Scopus
  29. I. Grundke-Iqbal, K. Iqbal, and Y. C. Tung, “Abnormal phosphorylation of the microtubule-associated protein τ (tau) in Alzheimer cytoskeletal pathology,” Proceedings of the National Academy of Sciences of the United States of America, vol. 83, no. 13, pp. 44913–4917, 1986. View at Google Scholar · View at Scopus
  30. I. Grundke-Iqbal, K. Iqbal, and M. Quinlan, “Microtubule-associated protein tau. A component of Alzheimer paired helical filaments,” Journal of Biological Chemistry, vol. 261, no. 13, pp. 6084–6089, 1986. View at Google Scholar · View at Scopus
  31. K. S. Kosik, C. L. Joachim, and D. J. Selkoe, “Microtubule-associated protein tau (τ) is a major antigenic component of paired helical filaments in Alzheimer disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 83, no. 11, pp. 4044–4048, 1986. View at Google Scholar · View at Scopus
  32. M. D. Weingarten, A. H. Lockwood, S. Y. Hwo, and M. W. Kirschner, “A protein factor essential for microtubule assembly,” Proceedings of the National Academy of Sciences of the United States of America, vol. 72, no. 5, pp. 1858–1862, 1975. View at Google Scholar · View at Scopus
  33. P. Seubert, M. Mawal-Dewan, R. Barbour et al., “Detection of phosphorylated Ser in fetal tau, adult tau, and paired helical filament tau,” Journal of Biological Chemistry, vol. 270, no. 32, pp. 18917–18922, 1995. View at Publisher · View at Google Scholar · View at Scopus
  34. A. Harada, K. Oguchi, S. Okabe et al., “Altered microtubule organization in small-calibre axons of mice lacking tau protein,” Nature, vol. 369, no. 6480, pp. 488–491, 1994. View at Publisher · View at Google Scholar · View at Scopus
  35. G. T. Bramblett, M. Goedert, R. Jakes, S. E. Merrick, J. Q. Trojanowski, and V. M. Y. Lee -, “Abnormal tau phosphorylation at Ser396 in Alzheimer's disease recapitulates development and contributes to reduced microtubule binding,” Neuron, vol. 10, no. 6, pp. 1089–1099, 1993. View at Publisher · View at Google Scholar · View at Scopus
  36. V. M. Y. Lee, M. Goedert, and J. Q. Trojanowski, “Neurodegenerative tauopathies,” Annual Review of Neuroscience, vol. 24, pp. 1121–1159, 2001. View at Publisher · View at Google Scholar · View at Scopus
  37. W. Sun, H. Y. Qureshi, P. W. Cafferty et al., “Glycogen synthase kinase-3β is complexed with tau protein in brain microtubules,” Journal of Biological Chemistry, vol. 277, no. 14, pp. 11933–11940, 2002. View at Publisher · View at Google Scholar · View at Scopus
  38. I. Ferrer, M. Barrachina, and B. Puig, “Glycogen synthase kinase-3 is associated with neuronal and glial hyperphosphorylated tau deposits in Alzheimer's diasese, Pick's disease, progressive supranuclear palsy and corticobasal degeneration,” Acta Neuropathologica, vol. 104, no. 6, pp. 583–591, 2002. View at Google Scholar · View at Scopus
  39. H. Yamaguchi, K. Ishiguro, T. Uchida, A. Takashima, C. A. Lemere, and K. Imahori, “Preferential labeling of Alzheimer neurofibrillary tangles with antisera for tau protein kinase (TPK) I/glycogen synthase kinase-3β and cyclin-dependent kinase 5, a component of TPK II,” Acta Neuropathologica, vol. 92, no. 3, pp. 232–241, 1996. View at Publisher · View at Google Scholar · View at Scopus
  40. D. P. Hanger, K. Hughes, J. R. Woodgett, J. P. Brion, and B. H. Anderton, “Glycogen synthase kinase-3 induces Alzheimer's disease-like phosphorylation of tau: generation of paired helical filament epitopes and neuronal localisation of the kinase,” Neuroscience Letters, vol. 147, no. 1, pp. 58–62, 1992. View at Publisher · View at Google Scholar · View at Scopus
  41. E. M. Mandelkow, G. Drewes, J. Biernat et al., “Glycogen synthase kinase-3 and the Alzheimer-like state of microtubule-associated protein tau,” FEBS Letters, vol. 314, no. 3, pp. 315–321, 1992. View at Publisher · View at Google Scholar · View at Scopus
  42. S. Lovestone, C. H. Reynolds, D. Latimer et al., “Alzheimer's disease-like phosphorylation of the microtubule-associated protein tau by glycogen synthase kinase-3 in transfected mammalian cells,” Current Biology, vol. 4, no. 12, pp. 1077–1086, 1994. View at Google Scholar · View at Scopus
  43. F. J. Moreno, M. Medina, M. Perez, E. Montejo De Garcini, and J. Avila, “Glycogen synthase kinase 3 phosphorylates recombinant human tau protein at serine-262 in the presence of heparin (or tubulin),” FEBS Letters, vol. 372, no. 1, pp. 65–68, 1995. View at Publisher · View at Google Scholar · View at Scopus
  44. B. R. Sperbera, S. Leight, M. Goedert, and V. M. Lee, “Glycogen synthase kinase-3β phosphorylates tau protein at multiple sites in intact cells,” Neuroscience Letters, vol. 197, no. 2, pp. 149–153, 1995. View at Publisher · View at Google Scholar
  45. T. Li and H. K. Paudel, “Glycogen synthase kinase 3β phosphorylates Alzheimer's disease-specific Ser396 of microtubule-associated protein tau by a sequential mechanism,” Biochemistry, vol. 45, no. 10, pp. 3125–3133, 2006. View at Publisher · View at Google Scholar · View at Scopus
  46. J. Brownlees, N. G. Irving, J. P. Brion et al., “Tau phosphorylation in transgenic mice expressing glycogen synthase kinase-3β transgenes,” NeuroReport, vol. 8, no. 15, pp. 3251–3255, 1997. View at Google Scholar · View at Scopus
  47. J. J. Lucas, F. Hernández, P. Gómez-Ramos, M. A. Morán, R. Hen, and J. Avila, “Decreased nuclear β-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3β conditional transgenic mice,” The EMBO Journal, vol. 20, no. 1-2, pp. 27–39, 2001. View at Publisher · View at Google Scholar · View at Scopus
  48. T. Engel, P. Goñi-Oliver, P. Gomez-Ramos et al., “Hippocampal neuronal subpopulations are differentially affected in double transgenic mice overexpressing frontotemporal dementia and parkinsonism linked to chromosome 17 tau and glycogen synthase kinase-3β,” Neuroscience, vol. 157, no. 4, pp. 772–780, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. K. Spittaels, C. van den Haute, J. van Dorpe et al., “Glycogen synthase kinase-3β phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice,” Journal of Biological Chemistry, vol. 275, no. 52, pp. 41340–41349, 2000. View at Publisher · View at Google Scholar · View at Scopus
  50. T. M. Malm, H. Iivonen, G. Goldsteins et al., “Pyrrolidine dithiocarbamate activates Akt and improves spatial learning in APP/PS1 mice without affecting β-amyloid burden,” Journal of Neuroscience, vol. 27, no. 14, pp. 3712–3721, 2007. View at Publisher · View at Google Scholar · View at Scopus
  51. H. R. Shi, L. Q. Zhu, S. H. Wang et al., “17β-estradiol attenuates glycogen synthase kinase-3β activation and tau hyperphosphorylation in Akt-independent manner,” Journal of Neural Transmission, vol. 115, no. 6, pp. 879–888, 2008. View at Publisher · View at Google Scholar · View at Scopus
  52. Z. Zhang, R. Zhao, J. Qi, S. Wen, Y. Tang, and D. Wang, “Inhibition of glycogen synthase kinase-3β by Angelica sinensis extract decreases β-amyloid-induced neurotoxicity and tau phosphorylation in cultured cortical neurons,” Journal of Neuroscience Research, vol. 89, no. 3, pp. 437–447, 2011. View at Publisher · View at Google Scholar
  53. M. Takahashi, K. Yasutake, and K. Tomizawa, “Lithium inhibits neurite growth and tau protein kinase I/glycogen synthase kinase-3β-dependent phosphorylation of juvenile tau in cultured hippocampal neurons,” Journal of Neurochemistry, vol. 73, no. 5, pp. 2073–2083, 1999. View at Google Scholar · View at Scopus
  54. S. Leclerc, M. Garnier, R. Hoessel et al., “Indirubins inhibit glycogen synthase kinase-3β and CDK5/P25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer's disease. A property common to most cyclin-dependent kinase inhibitors?” Journal of Biological Chemistry, vol. 276, no. 1, pp. 251–260, 2001. View at Publisher · View at Google Scholar · View at Scopus
  55. W. Noble, E. Planel, C. Zehr et al., “Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 19, pp. 6990–6995, 2005. View at Publisher · View at Google Scholar · View at Scopus
  56. A. P. Kozikowski, I. N. Gaisina, P. A. Petukhov et al., “Highly potent and specific GSK-3β inhibitors that block tau phosphorylation and decrease α-synuclein protein expression in a cellular model of Parkinson's disease,” ChemMedChem, vol. 1, no. 2, pp. 256–266, 2006. View at Publisher · View at Google Scholar · View at Scopus
  57. S. J. Greco, S. Sarkar, G. Casadesus et al., “Leptin inhibits glycogen synthase kinase-3β to prevent tau phosphorylation in neuronal cells,” Neuroscience Letters, vol. 455, no. 3, pp. 191–194, 2009. View at Publisher · View at Google Scholar · View at Scopus
  58. P. J. Crouch, W. H. Lin, P. A. Adlard et al., “Increasing Cu bioavailability inhibits Aβ oligomers and tau phosphorylation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 2, pp. 381–386, 2009. View at Publisher · View at Google Scholar · View at Scopus
  59. S. Lovestone, C. L. Hartley, J. Pearce, and B. H. Anderton, “Phosphorylation of tau by glycogen synthase kinase-3β in intact mammalian cells: the effects on the organization and stability of microtubules,” Neuroscience, vol. 73, no. 4, pp. 1145–1157, 1996. View at Publisher · View at Google Scholar · View at Scopus
  60. H. Sang, Z. Lu, Y. Li, B. Ru, W. Wang, and J. Chen, “Phosphorylation of tau by glycogen synthase kinase 3β in intact mammalian cells influences the stability of microtubules,” Neuroscience Letters, vol. 312, no. 3, pp. 141–144, 2001. View at Publisher · View at Google Scholar · View at Scopus
  61. M. A. Utton, A. Vandecandelaere, U. Wagner et al., “Phosphorylation of tau by glycogen synthase kinase 3β affects the ability of tau to promote microtubule self-assembly,” Biochemical Journal, vol. 323, no. 3, pp. 741–747, 1997. View at Google Scholar · View at Scopus
  62. J. H. Cho and G. V. W. Johnson, “Glycogen synthase kinase 3β phosphorylates tau at both primed and unprimed sites: differential impact on microtubule binding,” Journal of Biological Chemistry, vol. 278, no. 1, pp. 187–193, 2003. View at Publisher · View at Google Scholar · View at Scopus
  63. K. Leroy, R. Menu, J. L. Conreur et al., “The function of the microtubule-associated protein tau is variably modulated by graded changes in glycogen synthase kinase-3β activity,” FEBS Letters, vol. 465, no. 1, pp. 34–38, 2000. View at Publisher · View at Google Scholar · View at Scopus
  64. Y. Tatebayashi, N. Haque, Y. C. Tung, K. Iqbal, and I. Grundke-Iqbal, “Role of tau phosphorylation by glycogen synthase kinase-3β in the regulation of organelle transport,” Journal of Cell Science, vol. 117, no. 9, pp. 1653–1663, 2004. View at Publisher · View at Google Scholar · View at Scopus
  65. I. Cuchillo-Ibanez, A. Seereeram, H. L. Byers et al., “Phosphorylation of tau regulates its axonal transport by controlling its binding to kinesin,” FASEB Journal, vol. 22, no. 9, pp. 3186–3195, 2008. View at Publisher · View at Google Scholar · View at Scopus
  66. J. Dill, H. Wang, F. Zhou, and S. Li, “Inactivation of glycogen synthase kinase 3 promotes axonal growth and recovery in the CNS,” Journal of Neuroscience, vol. 28, no. 36, pp. 8914–8928, 2008. View at Publisher · View at Google Scholar · View at Scopus
  67. S. B. Shim, H. J. Lim, K. R. Chae et al., “Tau overexpression in transgenic mice induces glycogen synthase kinase 3β and β-catenin phosphorylation,” Neuroscience, vol. 146, no. 2, pp. 730–740, 2007. View at Publisher · View at Google Scholar · View at Scopus
  68. J. H. Cho and G. V. W. Johnson, “Glycogen synthase kinase 3β induces caspase-cleaved tau aggregation in situ,” Journal of Biological Chemistry, vol. 279, no. 52, pp. 54716–54723, 2004. View at Publisher · View at Google Scholar · View at Scopus
  69. J. H. Peng, C. E. Zhang, W. Wei, X. P. Hong, XI. P. Pan, and J. Z. Wang, “Dehydroevodiamine attenuates tau hyperphosphorylation and spatial memory deficit induced by activation of glycogen synthase kinase-3 in rats,” Neuropharmacology, vol. 52, no. 7, pp. 1521–1527, 2007. View at Publisher · View at Google Scholar · View at Scopus
  70. W. Chun and G. V. W. Johnson, “Activation of glycogen synthase kinase 3β promotes the intermolecular association of tau: the use of fluorescence resonance energy transfer microscopy,” Journal of Biological Chemistry, vol. 282, no. 32, pp. 23410–23417, 2007. View at Publisher · View at Google Scholar · View at Scopus
  71. T. Engel, J. J. Lucas, P. Gómez-Ramos, M. A. Moran, J. Ávila, and F. Hernández, “Cooexpression of FTDP-17 tau and GSK-3β in transgenic mice induce tau polymerization and neurodegeneration,” Neurobiology of Aging, vol. 27, no. 9, pp. 1258–1268, 2006. View at Publisher · View at Google Scholar · View at Scopus
  72. T. Engel, F. Hernández, J. Avila, and J. J. Lucas, “Full reversal of Alzheimer's disease-like phenotype in a mouse model with conditional overexpression of glycogen synthase kinase-3,” Journal of Neuroscience, vol. 26, no. 19, pp. 5083–5090, 2006. View at Publisher · View at Google Scholar · View at Scopus
  73. M. Pérez, F. Hernández, F. Lim, J. Díaz-Nido, and J. Avila, “Chronic lithium treatment decreases mutant tau protein aggregation in a transgenic mouse model,” Journal of Alzheimer's Disease, vol. 5, no. 4, pp. 301–308, 2003. View at Google Scholar · View at Scopus
  74. H. Nakashima, T. Ishihara, P. Suguimoto et al., “Chronic lithium treatment decreases tau lesions by promoting ubiquitination in a mouse model of tauopathies,” Acta Neuropathologica, vol. 110, no. 6, pp. 547–556, 2005. View at Publisher · View at Google Scholar · View at Scopus
  75. T. Engel, P. Goñi-Oliver, J. J. Lucas, J. Avila, and F. Hernández, “Chronic lithium administration to FTDP-17 tau and GSK-3β overexpressing mice prevents tau hyperphosphorylation and neurofibrillary tangle formation, but pre-formed neurofibrillary tangles do not revert,” Journal of Neurochemistry, vol. 99, no. 6, pp. 1445–1455, 2006. View at Publisher · View at Google Scholar · View at Scopus
  76. E. Gómez de Barreda, M. Pérez, P. Gómez Ramos et al., “Tau-knockout mice show reduced GSK3-induced hippocampal degeneration and learning deficits,” Neurobiology of Disease, vol. 37, no. 3, pp. 622–629, 2010. View at Publisher · View at Google Scholar · View at Scopus
  77. F. Hernández, M. Pérez, J. J. Lucas, A. M. Mata, R. Bhat, and J. Avila, “Glycogen synthase kinase-3 plays a crucial role in tau exon 10 splicing and intranuclear distribution of SC35: implications for Alzheimer's disease,” Journal of Biological Chemistry, vol. 279, no. 5, pp. 3801–3806, 2004. View at Publisher · View at Google Scholar · View at Scopus
  78. L. Martin, A. Magnaudeix, F. Esclaire, C. Yardin, and F. Terro, “Inhibition of glycogen synthase kinase-3β downregulates total tau proteins in cultured neurons and its reversal by the blockade of protein phosphatase-2A,” Brain Research, vol. 1252, no. C, pp. 66–75, 2009. View at Publisher · View at Google Scholar · View at Scopus
  79. A. Rametti, F. Esclaire, C. Yardin, N. Cogné, and F. Terro, “Lithium down-regulates tau in cultured cortical neurons: a possible mechanism of neuroprotection,” Neuroscience Letters, vol. 434, no. 1, pp. 93–98, 2008. View at Publisher · View at Google Scholar · View at Scopus
  80. J. Götz, F. Chen, J. van Dorpe, and R. M. Nitsch, “Formation of neurofibrillary tangles in P301L tau transgenic mice induced by Aβ42 fibrils,” Science, vol. 293, no. 5534, pp. 1491–1495, 2001. View at Publisher · View at Google Scholar · View at Scopus
  81. S. Melov, P. A. Adlard, K. Morten et al., “Mitochondrial oxidative stress causes hyperphosphorylation of tau,” PLoS ONE, vol. 2, no. 6, article e536, 2007. View at Publisher · View at Google Scholar · View at Scopus
  82. A. Takashima, K. Noguchi, K. Sato, T. Hoshino, and K. Imahori, “Tau protein kinase I is essential for amyloid β-protein-induced neurotoxicity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 16, pp. 7789–7793, 1993. View at Google Scholar · View at Scopus
  83. A. Takashima, K. Noguchi, G. Michel et al., “Exposure of rat hippocampal neurons to amyloid β peptide (25–35) induces the inactivation of phosphatidyl inositol-3 kinase and the activation of tau protein kinase I/glycogen synthase kinase-3β,” Neuroscience Letters, vol. 203, no. 1, pp. 33–36, 1996. View at Publisher · View at Google Scholar · View at Scopus
  84. M. Hoshi, M. Sato, S. Matsumoto et al., “Spherical aggregates of β-amyloid (amylospheroid) show high neurotoxicity and activate tau protein kinase I/glycogen synthase kinase-3β,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 11, pp. 6370–6375, 2003. View at Publisher · View at Google Scholar · View at Scopus
  85. Q.-L. Ma, G. P. Lim, M. E. Harris-White et al., “Antibodies against β-amyloid reduce Aβ oligomers, glycogen synthase kinase-3β activation and τ phosphorylation in vivo and in vitro,” Journal of Neuroscience Research, vol. 83, no. 3, pp. 374–384, 2006. View at Publisher · View at Google Scholar
  86. A. Takashima, T. Honda, K. Yasutake et al., “Activation of tau protein kinase I/glycogen synthase kinase-3β by amyloid β peptide (25–35) enhances phosphorylation of tau in hippocampal neurons,” Neuroscience Research, vol. 31, no. 4, pp. 317–323, 1998. View at Publisher · View at Google Scholar · View at Scopus
  87. A. E. Aplin, J. S. Jacobsen, B. H. Anderton, and J. M. Gallo, “Effect of increased glycogen synthase kinase-3 activity upon the maturation of the amyloid precursor protein in transfected cells,” NeuroReport, vol. 8, no. 3, pp. 639–643, 1997. View at Google Scholar · View at Scopus
  88. S. H. Koh, M. Y. Noh, and S. H. Kim, “Amyloid-beta-induced neurotoxicity is reduced by inhibition of glycogen synthase kinase-3,” Brain Research, vol. 1188, no. 1, pp. 254–262, 2008. View at Publisher · View at Google Scholar · View at Scopus
  89. D. Terwel, D. Muyllaert, I. Dewachter et al., “Amyloid activates GSK-3β to aggravate neuronal tauopathy in bigenic mice,” American Journal of Pathology, vol. 172, no. 3, pp. 786–798, 2008. View at Publisher · View at Google Scholar · View at Scopus
  90. K. Ghosal, D. L. Vogt, M. Liang, Y. Shen, B. T. Lamb, and S. W. Pimplikar, “Alzheimer's disease-like pathological features in transgenic mice expressing the APP intracellular domain,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 43, pp. 18367–18372, 2009. View at Publisher · View at Google Scholar · View at Scopus
  91. G. Amadoro, V. Corsetti, M. T. Ciotti et al., “Endogenous Aβ causes cell death via early tau hyperphosphorylation,” Neurobiology of Aging. In press. View at Publisher · View at Google Scholar · View at Scopus
  92. E. D. Roberson, K. Scearce-Levie, J. J. Palop et al., “Reducing endogenous tau ameliorates amyloid β-induced deficits in an Alzheimer's disease mouse model,” Science, vol. 316, no. 5825, pp. 750–754, 2007. View at Publisher · View at Google Scholar · View at Scopus
  93. L. M. Ittner, Y. D. Ke, F. Delerue et al., “Dendritic function of tau mediates amyloid-β toxicity in alzheimer's disease mouse models,” Cell, vol. 142, no. 3, pp. 387–397, 2010. View at Publisher · View at Google Scholar
  94. A. E. Aplin, G. M. Gibb, J. S. Jacobsen, J. M. Gallo, and B. H. Anderton, “In vitro phosphorylation of the cytoplasmic domain of the amyloid precursor protein by glycogen synthase kinase-3β,” Journal of Neurochemistry, vol. 67, no. 2, pp. 699–707, 1996. View at Google Scholar · View at Scopus
  95. C. Terracciano, A. Nogalska, W. K. Engel, and V. Askanas, “In APP-overexpressing cultured human muscle fibers proteasome inhibition enhances phosphorylation of APP751 and GSK3 activation: effects mitigated by lithium and apparently relevant to sporadic inclusion-body myositis,” Journal of Neurochemistry, vol. 112, no. 2, pp. 389–396, 2010. View at Publisher · View at Google Scholar · View at Scopus
  96. F. Kirschenbaum, S. C. Hsu, B. Cordell, and J. V. McCarthy, “Glycogen synthase kinase-3β regulates presenilin 1 C-terminal fragment levels,” Journal of Biological Chemistry, vol. 276, no. 33, pp. 30701–30707, 2001. View at Publisher · View at Google Scholar · View at Scopus
  97. F. Kirschenbaum, S. C. Hsu, B. Cordell, and J. V. McCarthy, “Substitution of a glycogen synthase kinase-3β phosphorylation site in presenilin 1 separates presenilin function from β-catenin signaling,” Journal of Biological Chemistry, vol. 276, no. 10, pp. 7366–7375, 2001. View at Publisher · View at Google Scholar · View at Scopus
  98. C. Twomey and J. V. McCarthy, “Presenilin-1 is an unprimed glycogen synthase kinase-3β substrate,” FEBS Letters, vol. 580, no. 17, pp. 4015–4020, 2006. View at Publisher · View at Google Scholar · View at Scopus
  99. C. J. Phiel, C. A. Wilson, V. M. Y. Lee, and P. S. Klein, “GSK-3α regulates production of Alzheimer's disease amyloid-β peptides,” Nature, vol. 423, no. 6938, pp. 435–439, 2003. View at Publisher · View at Google Scholar · View at Scopus
  100. J. Ryder, Y. Su, F. Liu, B. Li, Y. Zhou, and B. Ni, “Divergent roles of GSK3 and CDK5 in APP processing,” Biochemical and Biophysical Research Communications, vol. 312, no. 4, pp. 922–929, 2003. View at Publisher · View at Google Scholar · View at Scopus
  101. E. Rockenstein, M. Torrance, A. Adame et al., “Neuroprotective effects of regulators of the glycogen synthase kinase-3β signaling pathway in a transgenic model of Alzheimer's disease are associated with reduced amyloid precursor protein phosphorylation,” Journal of Neuroscience, vol. 27, no. 8, pp. 1981–1991, 2007. View at Publisher · View at Google Scholar · View at Scopus
  102. L. Serenó, M. Coma, M. Rodríguez et al., “A novel GSK-3β inhibitor reduces Alzheimer's pathology and rescues neuronal loss in vivo,” Neurobiology of Disease, vol. 35, no. 3, pp. 359–367, 2009. View at Publisher · View at Google Scholar · View at Scopus
  103. H. Decker, K. Y. Lo, S. M. Unger, S. T. Ferreira, and M. A. Silverman, “Amyloid-β peptide oligomers disrupt axonal transport through an NMDA receptor-dependent mechanism that is mediated by glycogen synthase kinase 3β in primary cultured hippocampal neurons,” Journal of Neuroscience, vol. 30, no. 27, pp. 9166–9171, 2010. View at Publisher · View at Google Scholar
  104. M. R. Cookson, “The biochemistry of Parkinson's disease,” Annual Review of Biochemistry, vol. 74, pp. 29–52, 2005. View at Publisher · View at Google Scholar
  105. P. Lei, S. Ayton, D. I. Finkelstein, P. A. Adlard, C. L. Masters, and A. I. Bush, “Tau protein: relevance to Parkinson's disease,” International Journal of Biochemistry and Cell Biology, vol. 42, no. 11, pp. 1775–1778, 2010. View at Publisher · View at Google Scholar
  106. J. Simón-Sánchez, C. Schulte, J. M. Bras et al., “Genome-wide association study reveals genetic risk underlying Parkinson's disease,” Nature Genetics, vol. 41, no. 12, pp. 1308–1312, 2009. View at Publisher · View at Google Scholar · View at Scopus
  107. T. L. Edwards, W. K. Scott, C. Almonte et al., “Genome-Wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for parkinson disease,” Annals of Human Genetics, vol. 74, no. 2, pp. 97–109, 2010. View at Publisher · View at Google Scholar · View at Scopus
  108. M. Nagao and H. Hayashi, “Glycogen synthase kinase-3beta is associated with Parkinson's disease,” Neuroscience Letters, vol. 449, no. 2, pp. 103–107, 2009. View at Publisher · View at Google Scholar · View at Scopus
  109. J. Wills, J. Jones, T. Haggerty, V. Duka, J. N. Joyce, and A. Sidhu, “Elevated tauopathy and alpha-synuclein pathology in postmortem Parkinson's disease brains with and without dementia,” Experimental Neurology, vol. 225, no. 1, pp. 210–218, 2010. View at Publisher · View at Google Scholar
  110. T. Duka, V. Duka, J. N. Joyce, and A. Sidhu, “α-synuclein contributes to GSK-3β-catalyzed Tau phosphorylation in Parkinson's disease models,” FASEB Journal, vol. 23, no. 9, pp. 2820–2830, 2009. View at Publisher · View at Google Scholar · View at Scopus
  111. M. T. Armentero, E. Sinforiani, C. Ghezzi et al., “Peripheral expression of key regulatory kinases in Alzheimer's disease and Parkinson's disease,” Neurobiology of Aging. In press. View at Publisher · View at Google Scholar · View at Scopus
  112. J. B. J. Kwok, M. Hallupp, C. T. Loy et al., “GSK3B polymorphisms alter transcription and splicing in Parkinson's disease,” Annals of Neurology, vol. 58, no. 6, pp. 829–839, 2005. View at Publisher · View at Google Scholar · View at Scopus
  113. I. García-Gorostiaga, P. Sánchez-Juan, I. Mateo et al., “Glycogen synthase kinase-3β and tau genes interact in Parkinson's and Alzheimer's diseases,” Annals of Neurology, vol. 65, no. 6, pp. 759–761, 2009. View at Publisher · View at Google Scholar
  114. P. J. Khandelwal, S. B. Dumanis, L. R. Feng et al., “Parkinson-related parkin reduces α-synuclein phosphorylation in a gene transfer model,” Molecular Neurodegeneration, vol. 5, no. 1, p. 47, 2010. View at Publisher · View at Google Scholar
  115. W. Wang, Y. Yang, C. Ying et al., “Inhibition of glycogen synthase kinase-3β protects dopaminergic neurons from MPTP toxicity,” Neuropharmacology, vol. 52, no. 8, pp. 1678–1684, 2007. View at Publisher · View at Google Scholar · View at Scopus
  116. C. J. Phiel and P. S. Klein, “Molecular targets of lithium action,” Annual Review of Pharmacology and Toxicology, vol. 41, pp. 789–813, 2001. View at Publisher · View at Google Scholar · View at Scopus
  117. J. F. Cade, “Lithium salts in the treatment of psychotic excitement,” The Medical Journal of Australia, vol. 2, no. 10, pp. 349–352, 1949. View at Google Scholar
  118. K. N. Fountoulakis, E. Vieta, C. Bouras et al., “A systematic review of existing data on long-term lithium therapy: neuroprotective or neurotoxic?” International Journal of Neuropsychopharmacology, vol. 11, no. 2, pp. 269–287, 2008. View at Publisher · View at Google Scholar · View at Scopus
  119. W. T. O'Brien, A. D. Harper, F. Jové et al., “Glycogen synthase kinase-3β haploinsufficiency mimics the behavioral and molecular effects of lithium,” Journal of Neuroscience, vol. 24, no. 30, pp. 6791–6798, 2004. View at Publisher · View at Google Scholar · View at Scopus
  120. J. Prickaerts, D. Moechars, K. Cryns et al., “Transgenic mice overexpressing glycogen synthase kinase 3β: a putative model of hyperactivity and mania,” Journal of Neuroscience, vol. 26, no. 35, pp. 9022–9029, 2006. View at Publisher · View at Google Scholar
  121. P. S. Klein and D. A. Melton, “A molecular mechanism for the effect of lithium on development,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 16, pp. 8455–8459, 1996. View at Publisher · View at Google Scholar · View at Scopus
  122. W. J. Ryves and A. J. Harwood, “Lithium inhibits glycogen synthase kinase-3 by competition for magnesium,” Biochemical and Biophysical Research Communications, vol. 280, no. 3, pp. 720–725, 2001. View at Publisher · View at Google Scholar · View at Scopus
  123. E. Chalecka-Franaszek and DE. M. Chuang, “Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 15, pp. 8745–8750, 1999. View at Publisher · View at Google Scholar · View at Scopus
  124. P. De Sarno, X. Li, and R. S. Jope, “Regulation of Akt and glycogen synthase kinase-3β phosphorylation by sodium valproate and lithium,” Neuropharmacology, vol. 43, no. 7, pp. 1158–1164, 2002. View at Publisher · View at Google Scholar · View at Scopus
  125. C. M. Hedgepeth, L. J. Conrad, J. Zhang, H. C. Huang, V. M. Y. Lee, and P. S. Klein, “Activation of the Wnt signaling pathway: a molecular mechanism for lithium action,” Developmental Biology, vol. 185, no. 1, pp. 82–91, 1997. View at Publisher · View at Google Scholar · View at Scopus
  126. A. Caccamo, S. Oddo, L. X. Tran, and F. M. LaFerla, “Lithium reduces tau phosphorylation but not Aβ or working memory deficits in a transgenic model with both plaques and tangles,” American Journal of Pathology, vol. 170, no. 5, pp. 1669–1675, 2007. View at Publisher · View at Google Scholar · View at Scopus
  127. M. Hong, D. C. R. Chen, P. S. Klein, and V. M. Y. Lee, “Lithium reduces tau phosphorylation by inhibition of glycogen synthase kinase-3,” Journal of Biological Chemistry, vol. 272, no. 40, pp. 25326–25332, 1997. View at Publisher · View at Google Scholar · View at Scopus
  128. J. R. Muñoz-Montaño, F. J. Moreno, J. Avila, and J. Díaz-Nido, “Lithium inhibits Alzheimer's disease-like tau protein phosphorylation in neurons,” FEBS Letters, vol. 411, no. 2-3, pp. 183–188, 1997. View at Publisher · View at Google Scholar · View at Scopus
  129. S. Lovestone, D. R. Davis, M. T. Webster et al., “Lithium reduces tau phosphorylation: effects in living cells and in neurons at therapeutic concentrations,” Biological Psychiatry, vol. 45, no. 8, pp. 995–1003, 1999. View at Publisher · View at Google Scholar · View at Scopus
  130. X. Sun, S. Sato, O. Murayama et al., “Lithium inhibits amyloid secretion in COS7 cells transfected with amyloid precursor protein C100,” Neuroscience Letters, vol. 321, no. 1-2, pp. 61–64, 2002. View at Publisher · View at Google Scholar · View at Scopus
  131. Y. Su, J. Ryder, B. Li et al., “Lithium, a common drug for bipolar disorder treatment, regulates amyloid-β precursor protein processing,” Biochemistry, vol. 43, no. 22, pp. 6899–6908, 2004. View at Publisher · View at Google Scholar · View at Scopus
  132. C. Feyt, P. Kienlen-Campard, K. Leroy et al., “Lithium chloride increases the production of amyloid-β peptide independently from its inhibition of glycogen synthase kinase 3,” Journal of Biological Chemistry, vol. 280, no. 39, pp. 33220–33227, 2005. View at Publisher · View at Google Scholar · View at Scopus
  133. M. L. Selenica, H. S. Jensen, A. K. Larsen et al., “Efficacy of small-molecule glycogen synthase kinase-3 inhibitors in the postnatal rat model of tau hyperphosphorylation,” British Journal of Pharmacology, vol. 152, no. 6, pp. 959–979, 2007. View at Publisher · View at Google Scholar · View at Scopus
  134. E. Tsaltas, D. Kontis, V. Boulougouris et al., “Enhancing effects of chronic lithium on memory in the rat,” Behavioural Brain Research, vol. 177, no. 1, pp. 51–60, 2007. View at Publisher · View at Google Scholar · View at Scopus
  135. E. Tsaltas, T. Kyriazi, C. Poulopoulou, D. Kontis, and A. Maillis, “Enhancing effects of lithium on memory are not by-products of learning or attentional deficits,” Behavioural Brain Research, vol. 180, no. 2, pp. 241–245, 2007. View at Publisher · View at Google Scholar · View at Scopus
  136. O. Sofola, F. Kerr, I. Rogers et al., “Inhibition of GSK-3 ameliorates Aβ pathology in an adult-onset Drosophila model of Alzheimer's disease,” PLoS Genetics, vol. 6, no. 9, Article ID e1001087, 2010. View at Publisher · View at Google Scholar
  137. E. M. Toledo and N. C. Inestrosa, “Activation of Wnt signaling by lithium and rosiglitazone reduced spatial memory impairment and neurodegeneration in brains of an APPswe/PSEN1ΔE9 mouse model of Alzheimer's disease,” Molecular Psychiatry, vol. 15, no. 3, pp. 272–285, 2010. View at Publisher · View at Google Scholar
  138. A. Fiorentini, M. C. Rosi, C. Grossi, I. Luccarini, and F. Casamenti, “Lithium improves hippocampal neurogenesis, neuropathology and cognitive functions in APP mice,” PLoS ONE, vol. 5, no. 12, Article ID e14382, 2010. View at Publisher · View at Google Scholar
  139. K. Leroy, K. Ando, C. Héraud et al., “Lithium treatment arrests the development of neurofibrillary tangles in mutant tau transgenic mice with advanced neurofibrillary pathology,” Journal of Alzheimer's Disease, vol. 19, no. 2, pp. 705–719, 2010. View at Publisher · View at Google Scholar
  140. W. W. Havens and J. Cole, “Successful treatment of dementia with lithium,” Journal of Clinical Psychopharmacology, vol. 2, no. 1, pp. 71–72, 1982. View at Google Scholar · View at Scopus
  141. E. Tsaltas, D. Kontis, V. Boulougouris, and G. N. Papadimitriou, “Lithium and cognitive enhancement: leave it or take it?” Psychopharmacology, vol. 202, no. 1-3, pp. 457–476, 2009. View at Publisher · View at Google Scholar · View at Scopus
  142. P. V. Nunes, O. V. Forlenza, and W. F. Gattaz, “Lithium and risk for Alzheimer's disease in elderly patients with bipolar disorder,” British Journal of Psychiatry, vol. 190, pp. 359–360, 2007. View at Publisher · View at Google Scholar · View at Scopus
  143. T. Terao, H. Nakano, Y. Inoue, T. Okamoto, J. Nakamura, and N. Iwata, “Lithium and dementia: a preliminary study,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 30, no. 6, pp. 1125–1128, 2006. View at Publisher · View at Google Scholar · View at Scopus
  144. L. V. Kessing, J. L. Forman, and P. K. Andersen, “Does lithium protect against dementia?” Bipolar Disorders, vol. 12, no. 1, pp. 87–94, 2010. View at Publisher · View at Google Scholar · View at Scopus
  145. A. Macdonald, K. Briggs, M. Poppe, A. Higgins, L. Velayudhan, and S. Lovestone, “A feasibility and tolerability study of lithium in Alzheimer's disease,” International Journal of Geriatric Psychiatry, vol. 23, no. 7, pp. 704–711, 2008. View at Publisher · View at Google Scholar · View at Scopus
  146. N. Dunn, C. Holmes, and M. Mullee, “Does lithium therapy protect against the onset of dementia?” Alzheimer Disease and Associated Disorders, vol. 19, no. 1, pp. 20–22, 2005. View at Publisher · View at Google Scholar · View at Scopus
  147. H. Hampel, M. Ewers, K. Bürger et al., “Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study,” Journal of Clinical Psychiatry, vol. 70, no. 6, pp. 922–931, 2009. View at Publisher · View at Google Scholar · View at Scopus
  148. T. Leyhe, G. W. Eschweiler, E. Stransky et al., “Increase of bdnf serum concentration in lithium treated patients with early Alzheimer's disease,” Journal of Alzheimer's Disease, vol. 16, no. 3, pp. 649–656, 2009. View at Publisher · View at Google Scholar · View at Scopus
  149. M. B. H. Youdim and Z. Arraf, “Prevention of MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) dopaminergic neurotoxicity in mice by chronic lithium: involvements of Bcl-2 and Bax,” Neuropharmacology, vol. 46, no. 8, pp. 1130–1140, 2004. View at Publisher · View at Google Scholar · View at Scopus
  150. E. Friedman and S. Gershon, “Effect of lithium on brain dopamine,” Nature, vol. 243, no. 5409, pp. 520–521, 1973. View at Google Scholar · View at Scopus
  151. M. Dziedzicka-Wasylewska, M. Maćkowiak, K. Fijat, and K. Wędzony, “Adaptive changes in the rat dopaminergic transmission following repeated lithium administration,” Journal of Neural Transmission, vol. 103, no. 7, pp. 765–776, 1996. View at Publisher · View at Google Scholar · View at Scopus
  152. Y. Yong, H. Ding, Z. Fan, J. Luo, and Z.-J. Ke, “Lithium fails to protect dopaminergic neurons in the 6-ohda model of parkinson's disease,” Neurochemical Research, vol. 36, no. 3, pp. 367–374, 2010. View at Publisher · View at Google Scholar
  153. H. L. Feng, Y. Leng, C. H. Ma, J. Zhang, M. Ren, and D. M. Chuang, “Combined lithium and valproate treatment delays disease onset, reduces neurological deficits and prolongs survival in an amyotrophic lateral sclerosis mouse model,” Neuroscience, vol. 155, no. 3, pp. 567–572, 2008. View at Publisher · View at Google Scholar · View at Scopus
  154. F. Fornai, P. Longone, L. Cafaro et al., “Lithium delays progression of amyotrophic lateral sclerosis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 6, pp. 2052–2057, 2008. View at Publisher · View at Google Scholar · View at Scopus
  155. A. Gill, J. Kidd, F. Vieira, K. Thompson, and S. Perrin, “No benefit from chronic lithium dosing in a sibling-matched, gender balanced, investigator-blinded trial using a standard mouse model of familial ALS,” PLoS ONE, vol. 4, no. 8, Article ID e6489, 2009. View at Publisher · View at Google Scholar · View at Scopus
  156. S. P. Aggarwal, L. Zinman, E. Simpson et al., “Safety and efficacy of lithium in combination with riluzole for treatment of amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial,” The Lancet Neurology, vol. 9, no. 5, pp. 481–488, 2010. View at Publisher · View at Google Scholar · View at Scopus