Roles of glycogen synthase kinase 3 in Alzheimer's disease

Current Alzheimer Research

Volumn 9, Issue 7, 2012, Pages 864-879

  Cai, Zhiyou ^a,b   Zhao, Yu ^c   Zhao, Bin ^b  

^a TEXAS A AND M UNIVERSITY KINGSVILLE   (United States)

^b GUANGDONG MEDICAL UNIVERSITY   (China)

^c HARBIN MEDICAL UNIVERSITY   (China)

Author keywords

A ; Alzheimer's disease; Glycogen synthase kinase 3; Tau hyperphosphorylation

Indexed keywords

ALPHA SECRETASE; AMYLOID BETA PROTEIN; BETA SECRETASE; GAMMA SECRETASE; GLYCOGEN SYNTHASE KINASE 3; GLYCOGEN SYNTHASE KINASE 3 INHIBITOR; LITHIUM; PLACEBO; TAU PROTEIN; THIADIAZOLIDINONE DERIVATIVE; TIDEGLUSIB; UNCLASSIFIED DRUG; VALPROIC ACID;

ALZHEIMER DISEASE; ARTICLE; CHOLINERGIC SYSTEM; DELIRIUM; DRUG BLOOD LEVEL; DRUG EFFICACY; DRUG MECHANISM; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; HUMAN; LOW DRUG DOSE; NERVE CELL DEGENERATION; NERVE FIBER DEGENERATION; NERVE FIBER TRANSPORT; NERVOUS SYSTEM INFLAMMATION; NEUROFIBRILLARY TANGLE; OXIDATIVE STRESS; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; UNSPECIFIED SIDE EFFECT;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN PRECURSOR; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; BRAIN; GLYCOGEN SYNTHASE KINASE 3; HUMANS; NEUROFIBRILLARY TANGLES; PRESENILIN-1; TAU PROTEINS;

EID: 84865415419     PISSN: 15672050     EISSN: 18755828     Source Type: Journal    
DOI: 10.2174/156720512802455386     Document Type: Article

References (240)

1. Buoso E, Lanni C, Schettini G, Govoni S, Racchi M. beta-Amyloidprecursor protein metabolism: focus on the functions anddegradation of its intracellular domain. Pharmacol Res 62(4): 308-317 (2010).
2. Mancuso M, Orsucci D, LoGerfo A, Calsolaro V, Siciliano G. Clinical features and pathogenesis of Alzheimer's disease:involvement of mitochondria and mitochondrial DNA. Adv ExpMed Biol 685: 34-44 (2010).
3. Kawas CH, Corrada MM. Alzheimer's and dementia in the oldestold:a century of challenges. Curr Alzheimer Res 3(5): 411-419(2006).
4. Helzner EP, Scarmeas N, Cosentino S, Tang MX, Schupf N, SternY. Survival in Alzheimer disease: a multiethnic, population-basedstudy of incident cases. Neurology 271(19): 1489-1495 (2008).
5. Wilson RS, Weir DR, Leurgans SE, Evans DA, Hebert LE, LangaKM, et al. Sources of variability in estimates of the prevalence ofAlzheimer's disease in the United States. Alzheimers Dement 7(1):74-79 (2011).
6. Dhikav V, Anand K. Potential predictors of hippocampal atrophyin Alzheimer's disease. Drugs Aging 28(1): 1-11 (2011).
7. Vogel J, Anand VS, Ludwig B, Nawoschik S, Dunlop J, Braithwaite SP. The JNK pathway amplifies and drives subcellularchanges in tau phosphorylation. Neuropharmacology 57(5-6): 539-550 (2009).
8. Coralli MV, Zanotti E, Salsi A. [Current concepts on thehypothesis of the cholinergic etiology of Alzheimer's disease]. Recenti Prog Med 77(9): 436-439 (1986).
9. Bales KR, Tzavara ET, Wu S, Wade MR, Bymaster FP, Paul SM, et al. Cholinergic dysfunction in a mouse model of Alzheimerdisease is reversed by an anti-A beta antibody. J Clin Invest 116(3):825-832 (2006).
10. Sisodia SS, Price DL. Role of the beta-amyloid protein inAlzheimer's disease. FASEB J 9(5): 366-370 (1995).
11. Finder VH. Alzheimer's disease: a general introduction andpathomechanism. J Alzheimers Dis 22 (3): 5-19 (2010).
12. Price DL, Sisodia SS, Gandy SE. Amyloid beta amyloidosis inAlzheimer's disease. Curr Opin Neurol 8(4): 268-274 (1995).
13. Kurt MA, Davies DC, Kidd M. Paired helical filament morphologyvaries with intracellular location in Alzheimer's disease brain. Neurosci Lett 239(1): 41-44 (1997).
14. Eldar-Finkelman H, Licht-Murava A, Pietrokovski S, Eisenstein M. Substrate competitive GSK-3 inhibitors-strategy and implications. Biochim Biophys Acta 1804(3): 598-603 (2010).
15. Doble BW, Woodgett JR. GSK-3: tricks of the trade for a multitaskingkinase. J Cell Sci 116(Pt 7): 1175-1186 (2003).
16. Liss MA, Schlicht M, Kahler A, Fitzgerald R, Thomassi T, Degueme A, et al. Characterization of soy-based changes in Wntfrizzledsignaling in prostate cancer. Cancer Genomics Proteomics7(5): 245-252 (2010).
17. Quevedo C, Alcazar A, Salinas M. Two different signaltransduction pathways are implicated in the regulation of initiationfactor 2B activity in insulin-like growth factor-1-stimulatedneuronal cells. J Biol Chem 275(25): 19192-19197 (2000).
18. Longo KA, Kennell JA, Ochocinska MJ, Ross SE, Wright WS, MacDougald OA. Wnt signaling protects 3T3-L1 preadipocytesfrom apoptosis through induction of insulin-like growth factors. JBiol Chem 277(41): 38239-38244 (2002).
19. Forde JE, Dale TC. Glycogen synthase kinase 3: a key regulator ofcellular fate. Cell Mol Life Sci 64(15): 930-1944 (2007).
20. Sayas CL, Moreno-Flores MT, Avila J, Wandosell F. The neuriteretraction induced by lysophosphatidic acid increases Alzheimer'sdisease-like Tau phosphorylation. J Biol Chem 274(52): 37046-37052 (1999).
21. Ono M, Matsubara Y, Shibano T, Ikeda Y, Murata M. GSK-3betanegatively regulates megakaryocyte differentiation and plateletproduction from primary human bone marrow cells in vitro. Platelets 22(3):196-203 (2011).
22. Bhatia B, Nahle Z, Kenney AM. Double trouble: when sonichedgehog signaling meets TSC inactivation. Cell Cycle 9(3): 456-459 (2010).
23. Doble BW, Patel S, Wood GA, Kockeritz LK, Woodgett JR. Functional redundancy of GSK-3alpha and GSK-3beta inWnt/beta-catenin signaling shown by using an allelic series ofembryonic stem cell lines. Dev Cell 12(6): 957-971 (2007).
24. Takashima A. GSK-3 is essential in the pathogenesis ofAlzheimer's disease. J Alzheimers Dis 9(3): 309-317 (2006).
25. Ryder J, Su Y, Liu F, Li B, Zhou Y, Ni B. Divergent roles of GSK3and CDK5 in APP processing. Biochem Biophys Res Commun312(4): 922-929 (2003).
26. Hu S, Begum AN, Jones MR, Oh MS, Beech WK, Beech BH, et al. GSK3 inhibitors show benefits in an Alzheimer's disease (AD)model of neurodegeneration but adverse effects in control animals. Neurobiol Dis 33(2):193-206 (2009).
27. Huang HC, Klein PS. Multiple roles for glycogen synthase kinase-3 as a drug target in Alzheimer's disease. Curr Drug Targets 7(11):1389-1397 (2006).
28. Tsai JN, Lee CH, Jeng H, Chi WK, Chang WC. Differentialexpression of glycogen synthase kinase 3 genes during zebrafishembryogenesis. Mech Dev 91(1-2): 387-391 (2000).
29. Acevedo N, Wang X, Dunn RL, Smith GD. Glycogen synthasekinase-3 regulation of chromatin segregation and cytokinesis inmouse preimplantation embryos. Mol Reprod Dev 74(2): 178-188(2007).
30. Lee SC, Yang SD. Calphostin C induces tyrosinedephosphorylation/inactivation of protein kinase FA/GSK-3 alphain a pathway independent of tumor promoter phorbol estermediateddown-regulation of protein kinase C. J Cell Biochem60(1):121-129 (1996).
31. Blankesteijn WM, van de Schans VA, ter Horst P, Smits JF. TheWnt/frizzled/GSK-3 beta pathway: a novel therapeutic target forcardiac hypertrophy. Trends Pharmacol Sci 29(4):175-180 (2008).
32. Castano Z, Gordon-Weeks PR, Kypta RM. The neuron-specificisoform of glycogen synthase kinase-3beta is required for axongrowth. J Neurochem 113(1):117-130 (2010).
33. Wood-Kaczmar A, Kraus M, Ishiguro K, Philpott KL, Gordon-Weeks PR. An alternatively spliced form of glycogen synthasekinase-3beta is targeted to growing neurites and growth cones. MolCell Neurosci 42(3):184-194 (2009).
34. Saeki K, Machida M, Kinoshita Y, Takasawa R, Tanuma S. Glycogen synthase kinase-3beta2 has lower phosphorylationactivity to tau than glycogen synthase kinase-3beta1. Biol PharmBull 34(1): 146-149 (2011).
35. Ragano-Caracciolo M, Berlin WK, Miller MW, Hanover JA. Nuclear glycogen and glycogen synthase kinase 3. BiochemBiophys Res Commun 249(2): 422-427 (1998).
36. Nishino Y, Webb IG, Davidson SM, Ahmed AI, Clark JE, JacquetS, et al. Glycogen synthase kinase-3 inactivation is not required forischemic preconditioning or postconditioning in the mouse. CircRes 103(3): 307-314 (2008).
37. Campa VM, Kypta RM. Issues associated with the use ofphosphospecific antibodies to localise active and inactive pools ofGSK-3 in cells. Biol Direct 6(1): 4 (2011).
38. Wada A. GSK-3 inhibitors and insulin receptor signaling in health, disease, and therapeutics. Front Biosci 14: 1558-1570 (2009).
39. Nemoto T, Yanagita T, Kanai T, Wada A. Drug developmenttargeting the glycogen synthase kinase-3beta (GSK-3beta)-mediated signal transduction pathway: the role of GSK-3beta in themaintenance of steady-state levels of insulin receptor signalingmolecules and Na(v)1.7 sodium channel in adrenal chromaffincells. J Pharmacol Sci 109(2):157-161 (2009).
40. Jin T, George Fantus I, Sun J. Wnt and beyond Wnt: multiplemechanisms control the transcriptional property of beta-catenin. Cell Signal 20(10): 1697-1704 (2008).
41. Sakanaka C, Sun TQ, Williams LT. New steps in the Wnt/betacateninsignal transduction pathway. Recent Prog Horm Res 55:225-236 (2000).
42. Ikeda S, Kishida S, Yamamoto H, Murai H, Koyama S, Kikuchi A. Axin, a negative regulator of the Wnt signaling pathway, forms acomplex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. EMBO J17(5):1371-1384 (1998).
43. Topol L, Jiang X, Choi H, Garrett-Beal L, Carolan PJ, Yang Y. Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent beta-catenin degradation. J Cell Biol 162(5): 899-908(2003).
44. Popkie AP, Zeidner LC, Albrecht AM, D'Ippolito A, Eckardt S, Newsom DE, et al. Phosphatidylinositol 3-kinase (PI3K) signalingvia glycogen synthase kinase-3 (Gsk-3) regulates DNA methylationof imprinted loci. J Biol Chem 285(53): 41337-41347 (2010).
45. Murphy E, Steenbergen C. Inhibition of GSK-3beta as a target forcardioprotection: the importance of timing, location, duration anddegree of inhibition. Expert Opin Ther Targets 9(3): 447-456(2005)
46. Buescher JL, Phiel CJ. A noncatalytic domain of glycogen synthasekinase-3 (GSK-3) is essential for activity. J Biol Chem 285(11):7957-7963(2010).
47. Wang Q, Zhou Y, Wang X, Evers BM. Glycogen synthase kinase-3is a negative regulator of extracellular signal-regulated kinase. Oncogene 25(1): 43-50 (2006).
48. Pardo R, Andreolotti AG, Ramos B, Picatoste F, Claro E. Opposedeffects of lithium on the MEK-ERK pathway in neural cells:inhibition in astrocytes and stimulation in neurons by GSK3independent mechanisms. J Neurochem 87(2): 417-426 (2003).
49. Lochhead PA, Kinstrie R, Sibbet G, Rawjee T, Morrice N, CleghonV. A chaperone-dependent GSK3beta transitional intermediatemediates activation-loop autophosphorylation. Mol Cell 24(4):627-633 (2006).
50. Kang LJ, Lee HB, Bae HJ, Lee SG. Antidiabetic effect of propolis:reduction of expression of glucose-6-phosphatase throughinhibition of Y279 and Y216 autophosphorylation of GSK-3alpha/beta in HepG2 cells. Phytother Res 24(10): 1554-1561(2010).
51. Tuhackova Z, Sloncova E, Hlavacek J, Sovova V, Velek J. Activityof glycogen synthase kinase-3beta is down-regulated duringtransient differentiation of human colon cancer HT-29 cells. OncolRep 6(4): 827-832 (1999).
52. Fang X, Yu S, Tanyi JL, Lu Y, Woodgett JR, Mills GB. Convergence of multiple signaling cascades at glycogen synthasekinase 3: Edg receptor-mediated phosphorylation and inactivationby lysophosphatidic acid through a protein kinase C-dependentintracellular pathway. Mol Cell Biol 22(7): 2099-2110 (2002).
53. Kaidanovich O, Eldar-Finkelman H. The role of glycogen synthasekinase-3 in insulin resistance and type 2 diabetes. Expert Opin TherTargets 6(5): 555-561 (2002).
54. Kitagawa K, Hiramatsu Y, Uchida C, Isobe T, Hattori T, Oda T, etal. Fbw7 promotes ubiquitin-dependent degradation of c-Myb:involvement of GSK3-mediated phosphorylation of Thr-572 inmouse c-Myb. Oncogene 28(25): 2393-2405(2009).
55. Deldicque L, De Bock K, Maris M, Ramaekers M, Nielens H, Francaux M, et al. Increased p70(s6k) phosphorylation duringintake of a protein-carbohydrate drink following resistance exercisein the fasted state. Eur J Appl Physiol 108(4):791-800 (2010).
56. Hardt SE, Sadoshima J. Glycogen synthase kinase-3beta: a novelregulator of cardiac hypertrophy and development. Circ Res90(10): 1055-1063 (2002).
57. Sanchez C, Perez M, Avila J. GSK3beta-mediated phosphorylationof the microtubule-associated protein 2C (MAP2C) preventsmicrotubule bundling. Eur J Cell Biol 79(4): 252-260 (2000).
58. Belkhiri A, Dar AA, Zaika A, Kelley M, El-Rifai W. t-Darpppromotes cancer cell survival by up-regulation of Bcl2 throughAkt-dependent mechanism. Cancer Res 68(2): 395-403 (2008).
59. Phiel CJ, Wilson CA, Lee VM, Klein PS. GSK-3alpha regulatesproduction of Alzheimer's disease amyloid-beta peptides. Nature423(6938): 435-439 (2003).
60. Chen KL, Yuan RY, Hu CJ, Hsu CY. Amyloid-beta peptidealteration of tau exon-10 splicing via the GSK3beta-SC35 pathway. Neurobiol Dis 40(2): 378-385 (2010).
61. Kosuga S, Tashiro E, Kajioka T, Ueki M, Shimizu Y, Imoto M. GSK-3beta directly phosphorylates and activates MARK2/PAR-1. J Biol Chem 280(52): 42715-42722 (2005).
62. Gould TD, Manji HK. Glycogen synthase kinase-3: a putativemolecular target for lithium mimetic drugs. Neuropsychopharmacology 30(7): 1223-1237 (2005).
63. Giese KP. GSK-3: a key player in neurodegeneration and memory. IUBMB Life 61(5): 516-521 (2009).
64. Martinez A, Castro A, Dorronsoro I, Alonso M. Glycogen synthasekinase 3 (GSK-3) inhibitors as new promising drugs for diabetes, neurodegeneration, cancer, and inflammation. Med Res Rev 22(4):373-384(2002).
65. Li C, Zhao R, Gao K, Wei Z, Yin MY, Lau LT, et al. Astrocytes:implications for neuroinflammatory pathogenesis of Alzheimer'sdisease. Curr Alzheimer Res 8(1): 67-80 (2011).
66. Muyllaert D, Terwel D, Kremer A, Sennvik K, Borghgraef P, Devijver H, et al. Neurodegeneration and neuroinflammation incdk5/p25-inducible mice: a model for hippocampal sclerosis andneocortical degeneration. Am J Pathol 172(2): 470-485 (2008).
67. Wang Y, Huang WC, Wang CY, Tsai CC, Chen CL, Chang YT, etal. Inhibiting glycogen synthase kinase-3 reduces endotoxaemicacute renal failure by down-regulating inflammation and renal cellapoptosis. Br J Pharmacol 157(6): 1004-1013 (2009).
68. Cuzzocrea S, Crisafulli C, Mazzon E, Esposito E, Muia C, Abdelrahman M, et al. Inhibition of glycogen synthase kinase-3beta attenuates the development of carrageenan-induced lunginjury in mice. Br J Pharmacol 149(6):687-702 (2006).
69. Cacabelos R, Fernandez-Novoa L, Lombardi V, Kubota Y, TakedaM. Molecular genetics of Alzheimer's disease and aging. MethodsFind Exp Clin Pharmacol 27(A): 1-573 (2005).
70. Hernandez F, Gomez de Barreda E, Fuster-Matanzo A, Lucas JJ, Avila J. GSK3: a possible link between beta amyloid peptide andtau protein. Exp Neurol 223(2): 322-325 (2010).
71. Hernandez F, de Barreda EG, Fuster-Matanzo A, Goni-Oliver P, Lucas JJ, Avila J. The role of GSK3 in Alzheimer disease. BrainRes Bull 80(4-5): 248-250 (2009).
72. Hoshi M, Takashima A, Noguchi K, Murayama M, Sato M, KondoS, et al. Regulation of mitochondrial pyruvate dehydrogenaseactivity by tau protein kinase I/glycogen synthase kinase 3beta inbrain. Proc Natl Acad Sci USA 93(7): 2719-2723 (1996).
73. Forlenza OV, Spink JM, Dayanandan R, Anderton BH, Olesen OF, Lovestone S. Muscarinic agonists reduce tau phosphorylation innon-neuronal cells via GSK-3beta inhibition and in neurons. JNeural Transm 107(10): 1201-1212 (2000).
74. Smillie KJ, Cousin MA. The Role of GSK3 in PresynapticFunction. Int J Alzheimers Dis 2011: 263673 (2011).
75. Hernandez F, Avila J. The role of glycogen synthase kinase 3 in theearly stages of Alzheimers' disease. FEBS Lett 582(28): 3848-3854(2008).
76. Takashima A, Honda T, Yasutake K, Michel G, Murayama O, Murayama M, et al. Activation of tau protein kinase I/glycogensynthase kinase-3beta by amyloid beta peptide (25-35) enhancesphosphorylation of tau in hippocampal neurons. Neurosci Res31(4): 317-323 (1998).
77. Alvarez G, Munoz-Montano JR, Satrustegui J, Avila J, Bogonez E, Diaz-Nido J. Lithium protects cultured neurons against betaamyloid-induced neurodegeneration. FEBS Lett 453(3): 260-264(1999).
78. Petit-Paitel A. [GSK-3beta: a central kinase for neurodegenerativediseases?]. Med Sci (Paris) 26(5): 516-521 (2010).
79. Multhaup G. Amyloid precursor protein and BACE function asoligomers. Neurodegener Dis 3(4-5): 70-274 (2006).
80. Kojro E, Fahrenholz F. The non-amyloidogenic pathway: structureand function of alpha-secretases. Subcell Biochem 38: 105-127(2005).
81. Wolozin B, Bacic M, Merrill MJ, Lesch KP, Chen C, Lebovics RS, et al. Differential expression of carboxyl terminal derivatives ofamyloid precursor protein among cell lines. J Neurosci Res33(1):163-169 (1992).
82. Walter J, Haass C. Posttranslational modifications of amyloidprecursor protein: ectodomain phosphorylation and sulfation. Methods Mol Med 32: 149-168 (2000).
83. Santos SF, Tasiaux B, Sindic C, Octave JN. Inhibition of neuronalcalcium oscillations by cell surface APP phosphorylated on T668. Neurobiol Aging 32(12): 2308-13. (2011).
84. Knappenberger KS, Tian G, Ye X, Sobotka-Briner C, GhanekarSV, Greenberg BD, et al. Mechanism of gamma-secretase cleavageactivation: is gamma-secretase regulated through autoinhibitioninvolving the presenilin-1 exon 9 loop? Biochemistry 43(20): 6208-6218 (2004).
85. Muresan Z, Muresan V. Coordinated transport of phosphorylatedamyloid-beta precursor protein and c-Jun NH2-terminal kinaseinteractingprotein-1. J Cell Biol 171(4): 615-625 (2005).
86. Lee MS, Kao SC, Lemere CA, Xia W, Tseng HC, Zhou Y, et al. APP processing is regulated by cytoplasmic phosphorylation. J CellBiol 163(1): 83-95 (2003).
87. Su Y, Ryder J, Li B, Wu X, Fox N, Solenberg P, et al. Lithium, acommon drug for bipolar disorder treatment, regulates amyloidbeta precursor protein processing. Biochemistry 43(22): 6899-6908(2004).
88. Rezai-Zadeh K, Douglas Shytle R, Bai Y, Tian J, Hou H, Mori T, et al. Flavonoid-mediated presenilin-1 phosphorylation reducesAlzheimer's disease beta-amyloid production. J Cell Mol Med13(3): 574-588 (2009).
89. Hooper NM, Trew AJ, Parkin ET, Turner AJ. The role ofproteolysis in Alzheimer's disease. Adv Exp Med Biol 477: 379-390 (2000).
90. Hooper NM, Turner AJ. Protein processing mechanisms: fromangiotensin-converting enzyme to Alzheimer's disease. BiochemSoc Trans 28(4): 441-446 (2000).
91. Lammich S, Buell D, Zilow S, Ludwig AK, Nuscher B, Lichtenthaler SF, et al. Expression of the anti-amyloidogenicsecretase ADAM10 is suppressed by its 5'-untranslated region. JBiol Chem 285(21):15753-15760 (2010).
92. Allinson TM, Parkin ET, Turner AJ, Hooper NM. ADAMs familymembers as amyloid precursor protein alpha-secretases. J NeurosciRes 74(3): 342-352 (2003).
93. Hock C, Maddalena A, Heuser I, Naber D, Oertel W, von derKammer H, et al. Treatment with the selective muscarinic agonisttalsaclidine decreases cerebrospinal fluid levels of total amyloidbeta-peptide in patients with Alzheimer's disease. Ann NY AcadSci 920: 285-291 (2000).
94. Liskowsky W, Schliebs R. Muscarinic acetylcholine receptorinhibition in transgenic Alzheimer-like Tg2576 mice byscopolamine favours the amyloidogenic route of processing ofamyloid precursor protein. Int J Dev Neurosci 24(2-3): 149-156(2006).
95. Hooper NM, Turner AJ. The search for alpha-secretase and itspotential as a therapeutic approach to Alzheimer s disease. CurrMed Chem 9(11): 1107-1119 (2002).
96. Shepherd JD, Huganir RL. The cell biology of synaptic plasticity:AMPA receptor trafficking. Annu Rev Cell Dev Biol 23: 613-643(2007).
97. De Ferrari GV, Inestrosa NC. Wnt signaling function inAlzheimer's disease. Brain Res Brain Res Rev 33(1): 1-12 (2000).
98. Huse JT, Doms RW. Neurotoxic traffic: uncovering the mechanicsof amyloid production in Alzheimer's disease. Traffic 2(2): 75-81(2001).
99. Adachi A, Kano F, Saido TC, Murata M. Visual screening andanalysis for kinase-regulated membrane trafficking pathways thatare involved in extensive beta-amyloid secretion. Genes Cells14(3): 355-369 (2009).
100. Preece P, Virley DJ, Costandi M, Coombes R, Moss SJ, MudgeAW, et al. Beta-secretase (BACE) and GSK-3 mRNA levels inAlzheimer's disease. Brain Res Mol Brain Res 116(1-2): 155-158(2003).
101. Shi C, Zheng DD, Wu FM, Liu J, Xu J. The Phosphatidyl Inositol 3Kinase-Glycogen Synthase Kinase 3beta Pathway MediatesBilobalide-Induced Reduction in Amyloid beta-Peptide. Neurochem Res 37(2): 298-306 (2012).
102. Garrido JL, Godoy JA, Alvarez A, Bronfman M, Inestrosa NC. Protein kinase C inhibits amyloid beta peptide neurotoxicity byacting on members of the Wnt pathway. FASEB J 16(14): 1982-1984 (2002).
103. Winkler E, Hobson S, Fukumori A, Dumpelfeld B, Luebbers T, Baumann K, et al. Purification, pharmacological modulation, andbiochemical characterization of interactors of endogenous humangamma-secretase. Biochemistry 48(6): 1183-1197 (2009).
104. Wakabayashi T, De Strooper B. Presenilins: members of thegamma-secretase quartets, but part-time soloists too. Physiology(Bethesda) 23:194-204 (2008).
105. Tesco G, Tanzi RE. GSK3 beta forms a tetrameric complex withendogenous PS1-CTF/NTF and beta-catenin. Effects of theD257/D385A and FAD-linked mutations. Ann NY Acad Sci 920:227-232 (2000).
106. Twomey C, McCarthy JV. Presenilin-1 is an unprimed glycogensynthase kinase-3beta substrate. FEBS Lett 580(17): 4015-4020(2006).
107. Leng Y, Liang MH, Ren M, Marinova Z, Leeds P, Chuang DM. Synergistic neuroprotective effects of lithium and valproic acid orother histone deacetylase inhibitors in neurons: roles of glycogensynthase kinase-3 inhibition. J Neurosci 28(10): 2576-2588 (2008).
108. Qing H, He G, Ly PT, Fox CJ, Staufenbiel M, Cai F, et al. Valproicacid inhibits Abeta production, neuritic plaque formation, andbehavioral deficits in Alzheimer's disease mouse models. J ExpMed 205(12): 2781-2789 (2008).
109. Sereno L, Coma M, Rodriguez M, Sanchez-Ferrer P, Sanchez MB, Gich I, et al. A novel GSK-3beta inhibitor reduces Alzheimer'spathology and rescues neuronal loss in vivo. Neurobiol Dis 35(3):359-367 (2009).
110. Medina M, Avila J. Glycogen synthase kinase-3 (GSK-3) inhibitorsfor the treatment of Alzheimer's disease. Curr Pharm Des 16(25):2790-2798 (2010).
111. Panza F, Solfrizzi V, Frisardi V, Imbimbo BP, Capurso C, D'Introno A, et al. Beyond the neurotransmitter-focused approachin treating Alzheimer's disease: drugs targeting beta-amyloid andtau protein. Aging Clin Exp Res 21(6): 386-406 (2009).
112. Sofola O, Kerr F, Rogers I, Killick R, Augustin H, Gandy C, et al. Inhibition of GSK-3 ameliorates Abeta pathology in an adult-onsetDrosophila model of Alzheimer's disease. PLoS Genet 6(9): pii:e1001087 (2010).
113. Baki L, Neve RL, Shao Z, Shioi J, Georgakopoulos A, RobakisNK. Wild-type but not FAD mutant presenilin-1 prevents neuronaldegeneration by promoting phosphatidylinositol 3-kinaseneuroprotective signaling. J Neurosci 28(2): 483-490 (2008).
114. Baki L, Shioi J, Wen P, Shao Z, Schwarzman A, Gama-Sosa M, etal. PS1 activates PI3K thus inhibiting GSK-3 activity and tauoverphosphorylation: effects of FAD mutations. EMBO J 23(13):2586-2596 (2004).
115. Conboy L, Seymour CM, Monopoli MP, O'Sullivan NC, MurphyKJ, Regan CM. Notch signalling becomes transiently attenuatedduring long-term memory consolidation in adult Wistar rats. Neurobiol Learn Mem 88(3): 342-351 (2007).
116. Inestrosa NC, Varela-Nallar L, Grabowski CP, Colombres M. Synaptotoxicity in Alzheimer's disease: the Wnt signaling pathwayas a molecular target. IUBMB Life 59(4-5): 16-321 (2007).
117. Hofmann C, Dunger N, Scholmerich J, Falk W, Obermeier F. Glycogen synthase kinase 3-beta: a master regulator of toll-likereceptor-mediated chronic intestinal inflammation. Inflamm BowelDis 16(11): 1850-1858 (2010).
118. Erol A. Unraveling the molecular mechanisms behind themetabolic basis of sporadic Alzheimer's disease. J Alzheimers Dis17(2): 267-276 (2009).
119. Jope RS, Yuskaitis CJ, Beurel E. Glycogen synthase kinase-3(GSK3): inflammation, diseases, and therapeutics. Neurochem Res32(4-5): 577-595 (2007).
120. Beurel E, Jope RS. Glycogen synthase kinase-3 regulatesinflammatory tolerance in astrocytes. Neuroscience 169(3): 1063-1070 (2010).
121. Causevic M, Farooq U, Lovestone S, Killick R. beta-Amyloidprecursor protein and tau protein levels are differently regulated inhuman cerebellum compared to brain regions vulnerable toAlzheimer's type neurodegeneration. Neurosci Lett 485(3):162-166(2010).
122. Baum L, Masliah E, Iimoto DS, Hansen LA, Halliday WC, SaitohT. Casein kinase II is associated with neurofibrillary tangles but isnot an intrinsic component of paired helical filaments. Brain Res573(1): 126-132 (1992).
123. Muyllaert D, Kremer A, Jaworski T, Borghgraef P, Devijver H, Croes S, et al. Glycogen synthase kinase-3beta, or a link betweenamyloid and tau pathology? Genes Brain Behav 7(l): 57-66(2008).
124. Brion JP, Anderton BH, Authelet M, Dayanandan R, Leroy K, Lovestone S, et al. Neurofibrillary tangles and tau phosphorylation. Biochem Soc Symp (67): 81-88 (2001).
125. Brunden KR, Trojanowski JQ, Lee VM. Advances in tau-focuseddrug discovery for Alzheimer's disease and related tauopathies. NatRev Drug Discov 8(10): 783-793(2009).
126. Arendt T. Neurodegeneration and plasticity. Int J Dev Neurosci22(7): 507-514(2004).
127. Anthony IC, Norrby KE, Dingwall T, Carnie FW, Millar T, ArangoJC, et al. Predisposition to accelerated Alzheimer-related changesin the brains of human immunodeficiency virus negative opiateabusers. Brain 133(Pt 12): 3685-3698 (2010).
128. Pei JJ, Tanaka T, Tung YC, Braak E, Iqbal K, Grundke-Iqbal I. Distribution, levels, and activity of glycogen synthase kinase-3 inthe Alzheimer disease brain. J Neuropathol Exp Neurol 56(1): 70-78 (1997).
129. Peng JH, Zhang CE, Wei W, Hong XP, Pan XP, Wang JZ. Dehydroevodiamine attenuates tau hyperphosphorylation andspatial memory deficit induced by activation of glycogen synthasekinase-3 in rats. Neuropharmacology 52(7):1521-1527 (2007).
130. Qu ZS, Tian Q, Zhou XW, Wang Q, Zhang Q, Wang J. [Mechanism of tau hyperphosphorylation in brain cortex of diabeticrats and effect of LiCl]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao28(2): 244-248 (2006).
131. Brugg B, Matus A. Phosphorylation determines the binding ofmicrotubule-associated protein 2 (MAP2) to microtubules in livingcells. J Cell Biol 114(4): 735-743 (1999).
132. Anderton BH, Betts J, Blackstock WP, Brion JP, Chapman S, Connell J, et al. Sites of phosphorylation in tau and factorsaffecting their regulation. Biochem Soc Symp 67: 73-80 (2001).
133. Anderton BH, Brion JP, Couck AM, Davis DR, Gallo JM, HangerDP, et al. Modulation of PHF-like tau phosphorylation in culturedneurones and transfected cells. Neurobiol Aging 16(3): 389-397(1995).
134. Avila J, Hernandez F. GSK-3 inhibitors for Alzheimer's disease. Expert Rev Neurother 7(11): 1527-1533(2007).
135. Moreno FJ, Munoz-Montano JR, Avila J. Glycogen synthasekinase 3 phosphorylation of different residues in the presence ofdifferent factors: analysis on tau protein. Mol Cell Biochem 165(1):47-54 (1996).
136. Moreno FJ, Medina M, Perez M, Montejo de Garcini E, Avila J. Glycogen synthase kinase 3 phosphorylates recombinant human tauprotein at serine-262 in the presence of heparin (or tubulin). FEBSLett 372(1): 65-68 (1995).
137. Singh TJ, Grundke-Iqbal I, Iqbal K. Differential phosphorylation ofhuman tau isoforms containing three repeats by several proteinkinases. Arch Biochem Biophys 328(1): 43-50 (1996).
138. Hernandez F, Lucas JJ, Cuadros R, Avila J. GSK-3 dependentphosphoepitopes recognized by PHF-1 and AT-8 antibodies arepresent in different tau isoforms. Neurobiol Aging 24(8):1087-1094(2003).
139. Sun W, Qureshi HY, Cafferty PW, Sobue K, Agarwal-Mawal A, Neufield KD, et al. Glycogen synthase kinase-3beta is complexedwith tau protein in brain microtubules. J Biol Chem 277(14):11933-11940 (2002).
140. Ferrer I, Barrachina M, Puig B. Glycogen synthase kinase-3 isassociated with neuronal and glial hyperphosphorylated taudeposits in Alzheimer's disease, Pick's disease, progressivesupranuclear palsy and corticobasal degeneration. ActaNeuropathol 104(6): 583-591 (2002).
141. Ferrer I, Gomez-Isla T, Puig B, Freixes M, Ribe E, Dalfo E, et al. Current advances on different kinases involved in tauphosphorylation, and implications in Alzheimer's disease andtauopathies. Curr Alzheimer Res 2(1): 3-18 (2005).
142. Latimer DA, Gallo JM, Lovestone S, Miller CC, Reynolds CH, Marquardt B, et al. Stimulation of MAP kinase by v-raftransformation of fibroblasts fails to induce hyperphosphorylationof transfected tau. FEBS Lett 365(1):42-46 (1995).
143. Hernandez F, Perez M, Lucas JJ, Mata AM, Bhat R, Avila J. Glycogen synthase kinase-3 plays a crucial role in tau exon 10splicing and intranuclear distribution of SC35. Implications forAlzheimer's disease. J Biol Chem 279(5): 3801-3806 (2004).
144. Liu SJ, Zhang JY, Li HL, Fang ZY, Wang Q, Deng HM, et al. Taubecomes a more favorable substrate for GSK-3 when it isprephosphorylated by PKA in rat brain. J Biol Chem 279(48):50078-50088 (2004).
145. Lovestone S, Reynolds CH, Latimer D, Davis DR, Anderton BH, Gallo JM, et al. Alzheimer's disease-like phosphorylation of themicrotubule-associated protein tau by glycogen synthase kinase-3in transfected mammalian cells. Curr Biol 4(12): 1077-1086(1994).
146. Sengupta A, Grundke-Iqbal I, Iqbal K. Regulation ofphosphorylation of tau by protein kinases in rat brain. NeurochemRes 31(12): 1473-1480 (2006).
147. Singh TJ, Wang JZ, Novak M, Kontzekova E, Grundke-Iqbal I, Iqbal K. Calcium/calmodulin-dependent protein kinase IIphosphorylates tau at Ser-262 but only partially inhibits its bindingto microtubules. FEBS Lett 387(2-3): 145-148 (1996).
148. Singh TJ, Zaidi T, Grundke-Iqbal I, Iqbal K. Modulation of GSK-3-catalyzed phosphorylation of microtubule-associated protein tauby non-proline-dependent protein kinases. FEBS Lett 358(1): 4-8(1995).
149. Li X, Lu F, Tian Q, Yang Y, Wang Q, Wang JZ. Activation ofglycogen synthase kinase-3 induces Alzheimer-like tauhyperphosphorylation in rat hippocampus slices in culture. J NeuralTransm 113(1): 93-102 (2006).
150. Liu SJ, Zhang AH, Li HL, Wang Q, Deng HM, Netzer WJ, et al. Overactivation of glycogen synthase kinase-3 by inhibition ofphosphoinositol-3 kinase and protein kinase C leads tohyperphosphorylation of tau and impairment of spatial memory. JNeurochem 87(6): 1333-1344 (2003).
151. Lovestone S, Davis DR, Webster MT, Kaech S, Brion JP, Matus A, et al. Lithium reduces tau phosphorylation: effects in living cellsand in neurons at therapeutic concentrations. Biol Psychiatry 45(8):995-1003 (1999).
152. Wang JZ, Wu Q, Smith A, Grundke-Iqbal I, Iqbal K. Tau isphosphorylated by GSK-3 at several sites found in Alzheimerdisease and its biological activity markedly inhibited only after it isprephosphorylated by A-kinase. FEBS Lett 436(1): 28-34 (1998).
153. Li XH, Lv BL, Xie JZ, Liu J, Zhou XW, Wang JZ. AGEs induceAlzheimer-like tau pathology and memory deficit via RAGEmediatedGSK-3 activation. Neurobiol Aging 33(7): 1400-10(2012).
154. Singh TJ, Zaidi T, Grundke-Iqbal I, Iqbal K. Non-prolinedependentprotein kinases phosphorylate several sites found in taufrom Alzheimer disease brain. Mol Cell Biochem 154(2): 143-151(1996).
155. Sengupta A, Wu Q, Grundke-Iqbal I, Iqbal K, Singh TJ. Potentiation of GSK-3-catalyzed Alzheimer-like phosphorylationof human tau by cdk5. Mol Cell Biochem 167(1-2): 99-105 (1997).
156. Salminen A, Kauppinen A, Suuronen T, Kaarniranta K, Ojala J. ERstress in Alzheimer's disease: a novel neuronal trigger forinflammation and Alzheimer's pathology. J Neuroinflammation 6:41 (2009).
157. Martinez A, Perez DI. GSK-3 inhibitors: a ray of hope for thetreatment of Alzheimer's disease? J Alzheimers Dis 15(2): 181-191(2008).
158. Bamberger ME, Landreth GE. Inflammation, apoptosis, andAlzheimer's disease. Neuroscientist 8(3): 276-283 (2002).
159. Heneka MT, O'Banion MK. Inflammatory processes in Alzheimer'sdisease. J Neuroimmunol 184(1-2): 69-91 (2007).
160. Van Wauwe J, Haefner B. Glycogen synthase kinase-3 as drugtarget: from wallflower to center of attention. Drug News Perspect16(9): 557-565 (2003).
161. Aluise CD, Robinson RA, Beckett TL, Murphy MP, Cai J, PierceWM, et al. Preclinical Alzheimer disease: brain oxidative stress, Abeta peptide and proteomics. Neurobiol Dis 39(2): 221-228(2010).
162. De Felice FG, Velasco PT, Lambert MP, Viola K, Fernandez SJ, Ferreira ST, et al. Abeta oligomers induce neuronal oxidative stressthrough an N-methyl-D-aspartate receptor-dependent mechanismthat is blocked by the Alzheimer drug memantine. J Biol Chem282(15): 11590-11601 (2007).
163. Zilkova M, Zilka N, Kovac A, Kovacech B, Skrabana R, Skrabanova M, et al. Hyperphosphorylated truncated protein tauinduces caspase-3 independent apoptosis-like pathway in theAlzheimer's disease cellular model. J Alzheimers Dis 23(1): 161-169 (2011).
164. Tsukane M, Yoshizaki C, Yamauchi T. Development and specificinduction of apoptosis of cultured cell models overexpressinghuman tau during neural differentiation: Implication in Alzheimer'sdisease. Anal Biochem 360(1): 114-122 (2007).
165. Flirski M, Sobow T. Biochemical markers and risk factors ofAlzheimer's disease. Curr Alzheimer Res 2(1): 47-64(2005).
166. Miklossy J. Chronic inflammation and amyloidogenesis inAlzheimer's disease--role of Spirochetes. J Alzheimers Dis 13(4):381-391 (2008).
167. Messier C, Teutenberg K. The role of insulin, insulin growth factor, and insulin-degrading enzyme in brain aging and Alzheimer'sdisease. Neural Plast 12(4): 311-328 (2005).
168. Eldar-Finkelman, H. Glycogen synthase kinase 3: an emergingtherapeutic target. Trends Mol Med 8(3):126-132 (2002).
169. Plaschke K, Kopitz J, Siegelin M, Schliebs R, Salkovic-Petrisic M, Riederer P, et al. Insulin-resistant brain state afterintracerebroventricular streptozotocin injection exacerbatesAlzheimer-like changes in Tg2576 AbetaPP-overexpressing mice. JAlzheimers Dis 19(2): 691-704 (2010).
170. Sugano T, Yanagita T, Yokoo H, Satoh S, Kobayashi H, Wada A. Enhancement of insulin-induced PI3K/Akt/GSK-3beta and ERKsignaling by neuronal nicotinic receptor/PKC-alpha/ERK pathway:up-regulation of IRS-1/-2 mRNA and protein in adrenal chromaffincells. J Neurochem 98(1): 20-33 (2006).
171. Wang L, Yang HJ, Xia YY, Feng ZW. Insulin-like growth factor 1protects human neuroblastoma cells SH-EP1 against MPP+-induced apoptosis by AKT/GSK-3beta/JNK signaling. Apoptosis15(12):1470-1479 (2010).
172. Chong ZZ, Maiese K. Targeting WNT, protein kinase B, andmitochondrial membrane integrity to foster cellular survival in thenervous system. Histol Histopathol 19(2): 495-504 (2004).
173. Christian SL, Sims PV, Gold MR. The B cell antigen receptorregulates the transcriptional activator beta-catenin via proteinkinase C-mediated inhibition of glycogen synthase kinase-3. JImmunol 169(2): 758-769 (2002).
174. Alvarez AR, Godoy JA, Mullendorff K, Olivares GH, BronfmanM, Inestrosa NC. Wnt-3a overcomes beta-amyloid toxicity in rathippocampal neurons. Exp Cell Res 297(1): 186-196 (2004).
175. Caricasole A, Copani A, Caraci F, Aronica E, Rozemuller AJ, Caruso A, et al. Induction of Dickkopf-1, a negative modulator ofthe Wnt pathway, is associated with neuronal degeneration inAlzheimer's brain. J Neurosci 24(26): 6021-6027 (2004).
176. Caricasole A, Copani A, Caruso A, Caraci F, Iacovelli L, SortinoMA, et al. The Wnt pathway, cell-cycle activation and betaamyloid:novel therapeutic strategies in Alzheimer's disease?Trends Pharmacol Sci 24(5): 233-238 (2003).
177. Fuentealba LC, Eivers E, Ikeda A, Hurtado C, Kuroda H, Pera EM, et al. Integrating patterning signals: Wnt/GSK3 regulates theduration of the BMP/Smad1 signal. Cell 131(5): 980-993 (2007).
178. Ando K, Uemura K, Kuzuya A, Maesako M, Asada-Utsugi M, Kubota M, et al. N-cadherin regulates p38 MAPK signaling viaassociation with JNK-associated leucine zipper protein:implications for neurodegeneration in Alzheimer disease. J BiolChem 286(9): 7619-7628 (2011).
179. Origlia N, Arancio O, Domenici L, Yan SS. MAPK, beta-amyloidand synaptic dysfunction: the role of RAGE. Expert Rev Neurother9(11): 1635-1645 (2009).
180. Song JQ, Chen XC, Zhang J, Huang TW, Zeng YQ, Shen J, et al. [JNK/p38 MAPK involves in ginsenoside Rb1 attenuating betaamyloidpeptide (25-35)-induced tau protein hyperphosphorylationin embryo rat cortical neurons]. Yao Xue Xue Bao 43(1): 29-34(2008).
181. Reynolds CH, Nebreda AR, Gibb GM, Utton MA, Anderton BH. Reactivating kinase/p38 phosphorylates tau protein in vitro. JNeurochem 69(1): 191-198 (1997).
182. Zhu X, Lee HG, Raina AK, Perry G, Smith MA. The role ofmitogen-activated protein kinase pathways in Alzheimer's disease. Neurosignals 11(5): 270-281 (2002).
183. Zhu X, Castellani RJ, Takeda A, Nunomura A, Atwood CS, PerryG, et al. Differential activation of neuronal ERK, JNK/SAPK andp38 in Alzheimer disease: the 'two hit' hypothesis. Mech AgeingDev 123(1): 39-46 (2001).
184. Enguita M, DeGregorio-Rocasolano N, Abad A, Trullas R. Glycogen synthase kinase 3 activity mediates neuronal pentraxin 1expression and cell death induced by potassium deprivation incerebellar granule cells. Mol Pharmacol 67(4):1237-1246 (2005).
185. Whitehouse PJ, Price DL, Clark AW, Coyle JT, DeLong MR. Alzheimer disease: evidence for selective loss of cholinergicneurons in the nucleus basalis. Ann Neurol 10(2):122-126 (1981).
186. Plotkin DA, Jarvik LF. Cholinergic dysfunction in Alzheimerdisease: cause or effect? Prog Brain Res 65: 91-103 (1986).
187. Yates CM, Simpson J, Gordon A, Maloney AF, Allison Y, RitchieIM, et al. Catecholamines and cholinergic enzymes in pre-senileand senile Alzheimer-type dementia and Down's syndrome. BrainRes 280(1): 119-126 (1983).
188. Samadi A, Valderas C, de los Rios C, Bastida A, Chioua M, Gonzalez-Lafuente L, et al. Cholinergic and neuroprotective drugsfor the treatment of Alzheimer and neuronal vascular diseases. II. Synthesis, biological assessment, and molecular modelling of newtacrine analogues from highly substituted 2-aminopyridine-3-carbonitriles. Bioorg Med Chem 19(1): 122-133 (2011).
189. Wang H, Wang R, Zhao Z, Ji Z, Xu S, Holscher C, Sheng S. Coexistences of insulin signaling-related proteins and cholineacetyltransferase in neurons. Brain Res 1249: 237-243(2009).
190. De Sarno P, Bijur GN, Zmijewska AA, Li X, Jope RS. In vivoregulation of GSK3 phosphorylation by cholinergic and NMDAreceptors. Neurobiol Aging 27(3): 413-422 (2006).
191. Hawkes C, Jhamandas JH, Kar S. Selective loss of basal forebraincholinergic neurons by 192 IgG-saporin is associated withdecreased phosphorylation of Ser glycogen synthase kinase-3beta. JNeurochem 95(1): 263-272 (2005).
192. Bencherif M, Lippiello PM. Alpha7 neuronal nicotinic receptors:the missing link to understanding Alzheimer's etiopathology? MedHypotheses 74(2): 281-285 (2010).
193. Somogyi P, Freund TF, Cowey A. The axo-axonic interneuron inthe cerebral cortex of the rat, cat and monkey. Neuroscience 7(11):2577-2607 (1982).
194. Negishi M, Oinuma I, Katoh H. Plexins: axon guidance and signaltransduction. Cell Mol Life Sci 62(12):1363-1371 (2005).
195. Cancalon P. Influence of temperature on slow flow in populationsof regenerating axons with different elongation velocities. BrainRes 285(3): 279-289 (1983).
196. Edwards DH, Jr., Mulloney B. Synaptic integration in excitatoryand inhibitory crayfish motoneurons. J Neurophysiol 57(5):1425-1445 (1987).
197. Kokubo H, Kayed R, Glabe CG, Yamaguchi H. Soluble Abetaoligomers ultrastructurally localize to cell processes and might berelated to synaptic dysfunction in Alzheimer's disease brain. BrainRes 1031(2): 222-228 (2005).
198. Robert M, Mathuranath PS. Tau and tauopathies. Neurol India55(1): 11-16 (2007).
199. Sergeant N, Bretteville A, Hamdane M, Caillet-Boudin ML, Grognet P, Bombois S, et al. Biochemistry of Tau in Alzheimer'sdisease and related neurological disorders. Expert Rev Proteomics5(2): 207-224 (2008).
200. Rauk A. Why is the amyloid beta peptide of Alzheimer's diseaseneurotoxic? Dalton Trans (10): 1273-1282 (2008).
201. Adalbert R, Nogradi A, Babetto E, Janeckova L, Walker SA, Kerschensteiner M, et al. Severely dystrophic axons at amyloidplaques remain continuous and connected to viable cell bodies. Brain 132(Pt 2): 402-416 (2009).
202. Pope W, Enam SA, Bawa N, Miller BE, Ghanbari HA, Klein WL. Phosphorylated tau epitope of Alzheimer's disease is coupled toaxon development in the avian central nervous system. Exp Neurol120(1):106-113 (1993).
203. De Vos KJ, Grierson AJ, Ackerley S, Miller CC. Role of axonaltransport in neurodegenerative diseases. Annu Rev Neurosci31:151-173 (2008).
204. Geula C, Nagykery N, Nicholas A, Wu CK. Cholinergic neuronaland axonal abnormalities are present early in aging and inAlzheimer disease. J Neuropathol Exp Neurol 67(4): 309-318(2008).
205. Terry AV, Jr., Buccafusco JJ. The cholinergic hypothesis of ageand Alzheimer's disease-related cognitive deficits: recentchallenges and their implications for novel drug development. JPharmacol Exp Ther 306(3): 821-827 (2003).
206. Poon WW, Blurton-Jones M, Tu CH, Feinberg LM, Chabrier MA, Harris JW, Jeon NL, Cotman CW: beta-Amyloid impairs axonalBDNF retrograde trafficking. Neurobiol Aging 32(5): 821-833(2011).
207. Bartzokis G. Age-related myelin breakdown: a developmentalmodel of cognitive decline and Alzheimer's disease. NeurobiolAging 25(1): 5-18 (2004)
208. Bartzokis G, Lu PH, Mintz J. Quantifying age-related myelinbreakdown with MRI: novel therapeutic targets for preventingcognitive decline and Alzheimer's disease. J Alzheimers Dis 6(6Suppl): S53-59 (2004).
209. Bartzokis G, Beckson M, Lu PH, Edwards N, Rapoport R, BridgeP, Mintz J. Cortical gray matter volumes are associated withsubjective responses to cocaine infusion. Am J Addict 13(1): 64-73(2004).
210. Bartzokis G, Cummings JL, Sultzer D, Henderson VW, Nuechterlein KH, Mintz J. White matter structural integrity inhealthy aging adults and patients with Alzheimer disease: amagnetic resonance imaging study. Arch Neurol 60(3): 393-398(2003).
211. Bartzokis G. Alzheimer's disease as homeostatic responses to agerelatedmyelin breakdown. Neurobiol Aging 32(8):1341-71 (2011).
212. Garrido JJ, Simon D, Varea O, Wandosell F. GSK3 alpha andGSK3 beta are necessary for axon formation. FEBS Lett 581(8):1579-1586 (2007).
213. Alabed YZ, Pool M, Ong Tone S, Sutherland C, Fournier AE. GSK3 beta regulates myelin-dependent axon outgrowth inhibitionthrough CRMP4. J Neurosci 30(16): 5635-5643 (2010).
214. Kim WY, Zhou FQ, Zhou J, Yokota Y, Wang YM, Yoshimura T, et al. Essential roles for GSK-3s and GSK-3-primed substrates inneurotrophin-induced and hippocampal axon growth. Neuron52(6): 981-996 (2006).
215. Mudher A, Shepherd D, Newman TA, Mildren P, Jukes JP, SquireA, et al. GSK-3beta inhibition reverses axonal transport defects andbehavioural phenotypes in Drosophila. Mol Psychiatry 9(5): 522-530 (2004).
216. Yoshimura T, Kawano Y, Arimura N, Kawabata S, Kikuchi A, Kaibuchi K. GSK-3beta regulates phosphorylation of CRMP-2 andneuronal polarity. Cell 120(1):137-149 (2005).
217. Ni MH, Wu CC, Chan WH, Chien KY, Yu JS. GSK-3 mediates theokadaic acid-induced modification of collapsin response mediatorprotein-2 in human SK-N-SH neuroblastoma cells. J Cell Biochem103(6): 1833-1848 (2008).
218. Cole AR, Knebel A, Morrice NA, Robertson LA, Irving AJ, Connolly CN, et al. GSK-3 phosphorylation of the Alzheimerepitope within collapsin response mediator proteins regulates axonelongation in primary neurons. J Biol Chem 279(48): 50176-50180(2004).
219. Julien JP, Mushynski WE. Neurofilaments in health and disease. Prog Nucleic Acid Res Mol Biol 61: 1-23 (1998).
220. Gu Y, Hamajima N, Ihara Y. Neurofibrillary tangle-associatedcollapsin response mediator protein-2 (CRMP-2) is highlyphosphorylated on Thr-509, Ser-518, and Ser-522. Biochemistry39(15): 4267-4275 (2000).
221. Yoshimura T, Arimura N, Kaibuchi K. Molecular mechanisms ofaxon specification and neuronal disorders. Ann NY Acad Sci 1086:116-125 (2006).
222. Soutar MP, Kim WY, Williamson R, Peggie M, Hastie CJ, McLauchlan H, et al. Evidence that glycogen synthase kinase-3isoforms have distinct substrate preference in the brain. JNeurochem 115(4): 974-983 (2010).
223. Takashima A, Yamaguchi H, Noguchi K, Michel G, Ishiguro K, Sato K, et al. Amyloid beta peptide induces cytoplasmicaccumulation of amyloid protein precursor via tau protein kinaseI/glycogen synthase kinase-3 beta in rat hippocampal neurons. Neurosci Lett 198(2): 83-86 (1995).
224. Ryan KA, Pimplikar SW. Activation of GSK-3 andphosphorylation of CRMP2 in transgenic mice expressing APPintracellular domain. J Cell Biol 171(2): 327-335 (2005).
225. Pigino G, Morfini G, Pelsman A, Mattson MP, Brady ST, Busciglio J. Alzheimer's presenilin 1 mutations impair kinesinbasedaxonal transport. J Neurosci 23(11): 4499-4508 (2003).
226. Bellizzi MJ, Lu SM, Gelbard HA. Protecting the synapse: evidencefor a rational strategy to treat HIV-1 associated neurologic disease. J Neuroimmune Pharmacol 1(1): 20-31 (2006).
227. Abad MA, Enguita M, DeGregorio-Rocasolano N, Ferrer I, TrullasR. Neuronal pentraxin 1 contributes to the neuronal damage evokedby amyloid-beta and is overexpressed in dystrophic neurites inAlzheimer's brain. J Neurosci 26(49): 12735-12747 (2006).
228. Li S, Hong S, Shepardson NE, Walsh DM, Shankar GM, Selkoe D. Soluble oligomers of amyloid Beta protein facilitate hippocampallong-term depression by disrupting neuronal glutamate uptake. Neuron 62(6): 788-801 (2009).
229. Shonesy BC, Thiruchelvam K, Parameshwaran K, Rahman EA, Karuppagounder SS, Huggins KW, et al. Central insulin resistanceand synaptic dysfunction in intracerebroventricular-streptozotocininjected rodents. Neurobiol Aging 33(2): 430. e5-18. (2012).
230. Lauterbach EC, Victoroff J, Coburn KL, Shillcutt SD, Doonan SM, Mendez MF. Psychopharmacological neuroprotection inneurodegenerative disease: assessing the preclinical data. JNeuropsychiatry Clin Neurosci 22(1): 8-18 (2010).
231. Luna-Medina R, Cortes-Canteli M, Alonso M, Santos A, MartinezA, Perez-Castillo A. Regulation of inflammatory response in neuralcells in vitro by thiadiazolidinones derivatives through peroxisomeproliferator-activated receptor gamma activation. J Biol Chem280(22): 21453-21462 (2005).
232. Martinez A, Alonso M, Castro A, Perez C, Moreno FJ. First non-ATP competitive glycogen synthase kinase 3 beta (GSK-3beta)inhibitors: thiadiazolidinones (TDZD) as potential drugs for thetreatment of Alzheimer's disease. J Med Chem 45(6): 1292-1299(2002).
233. Hampel H, Ewers M, Burger K, Annas P, Mortberg A, Bogstedt A, et al. Lithium trial in Alzheimer's disease: a randomized, singleblind, placebo-controlled, multicenter 10-week study. J ClinPsychiatry 70(6): 922-931 (2009).
234. Pomara N. Lithium treatment in Alzheimer's disease does notpromote cognitive enhancement, but may exert long-termneuroprotective effects. Psychopharmacology (Berl) 205(1): 169-170 (2009).
235. Leyhe T, Eschweiler GW, Stransky E, Gasser T, Annas P, BasunH, et al. Increase of BDNF serum concentration in lithium treatedpatients with early Alzheimer's disease. J Alzheimers Dis 16(3):649-656 (2009).
236. Young W. Review of lithium effects on brain and blood. CellTransplant 18(9): 951-975 (2009).
237. Hull M, Berger M, Heneka M. Disease-modifying therapies inAlzheimer's disease: how far have we come? Drugs 66(16): 2075-2093 (2006).
238. Loy R, Tariot PN. Neuroprotective properties of valproate:potential benefit for AD and tauopathies. J Mol Neurosci 19(3):303-307 (2002).
239. Tariot PN. Valproate use in neuropsychiatric disorders in theelderly. Psychopharmacol Bull 37 (2): 116-128 (2003).
240. Hu JP, Xie JW, Wang CY, Wang T, Wang X, Wang SL, et al. Valproate reduces tau phosphorylation via cyclin-dependent kinase5 and glycogen synthase kinase 3 signaling pathways. Brain ResBull 85(3-4): 194-200 (2011).