Targeting the JAK2/STAT3 axis in Alzheimer's disease

Expert Opinion on Therapeutic Targets

Volumn 13, Issue 10, 2009, Pages 1155-1167

  Chiba, Tomohiro ^a   Yamada, Marina ^a   Aiso, Sadakazu ^a  

^a KEIO UNIVERSITY SCHOOL OF MEDICINE   (Japan)

Author keywords

Alzheimer's disease (AD); Colivelin (CLN); Humanin (HN); Janus kinase 2 (JAK2); Memory impairment; Neuroprotection; Signal transducer and activator of transcription 3 (STAT3)

Indexed keywords

COLIVELIN; GENOMIC DNA; GLUTAMYLPHENYLALANYLLEUCYLISOLEUCYLVALYLISOLEUCYLLYSYLSERYL METHIONYLALANYLPROLYLARGINYLGLYCYLPHENYLALANYLSERYLCYSTEINYLLEUCYLL EUCYLLEUCYLLEUCYLTHREONYLSERYLGLUTAMYLISOLEUCYLASPARTYLLEUCYL PROLYLVALYLLYSYLARGINYLARGINYLALANINE; HUMANIN; JANUS KINASE 2; METHIONYLALANYLPROLYLARGINYLGLYCYLPHENYLALANYLSERYL ALANYLLEUCYLLEUCYLLEUCYLLEUCYLTHREONYLSERYLGLUTAMYLISOLEUCYL ASPARTYLLEUCYLPROLYLVALYLLYSYLARGINYLARGINYLALANINE; METHIONYLALANYLPROLYLARGINYLGLYCYLPHENYLALANYLSERYL CYSTEINYLLEUCYLLEUCYLLEUCYLLEUCYLTHREONYLGLYCYLGLUTAMYLISOLEUCYL ASPARTYLLEUCYLPROLYLVALYLLYSYLARGINYLARGINYLARGININE; MITOCHONDRIAL DNA; NEUROPROTECTIVE AGENT; PROLYLALANYLGLYCYLALANYLSERYLARGINYLLEUCYLLEUCYLLEUCYLLEUCYL THREONYLGLYCYLGLUTAMYLISOLEUCYLASPARTYLLEUCYLPROLINE; PROLYLARGINYLGLYCYLPHENYLALANYLSERYLCYSTEINYLLEUCYLLEUCYLL EUCYLLEUCYLTHREONYLGLYCYLGLUTAMYLISOLEUCYLASPARTYLLEUCYLPROLINE; PROLYLARGINYLGLYCYLPHENYLALANYLSERYLCYSTEINYLLEUCYLLEUCYLL EUCYLLEUCYLTHREONYLSERYLGLUTAMYLISOLEUCYLASPARTYLLEUCYLPROLINE; RATTIN; STAT1 PROTEIN; STAT2 PROTEIN; STAT3 PROTEIN; STAT4 PROTEIN; STAT5A PROTEIN; STAT5B PROTEIN; STAT6 PROTEIN; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; AMINO ACID SEQUENCE; COGNITION; DOWN REGULATION; EXCITOTOXICITY; GENE EXPRESSION; HIPPOCAMPUS; HUMAN; IMMUNOHISTOCHEMISTRY; MEMORY DISORDER; NEUROPROTECTION; NONHUMAN; POSTSYNAPTIC POTENTIAL; PROTEIN PHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION;

ALZHEIMER DISEASE; HUMANS; JANUS KINASE 2; NEUROPROTECTIVE AGENTS; STAT3 TRANSCRIPTION FACTOR;

EID: 70349395723     PISSN: 14728222     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728220903213426     Document Type: Review

References (88)

1. Mattson MP. Pathways towards and away from Alzheimer's disease. Nature 2004;430(7000):631-639 (Pubitemid 39061671)
2. Bertram L, Tanzi RE. Thirty years of Alzheimer's disease genetics: the implications of systematic meta-analyses. Nat Rev Neurosci 2008;9(10):768-778
3. Chiba T, Nishimoto I, Aiso S, Matsuoka M. Neuroprotection against neurodegenerative diseases: development of a novel hybrid neuroprotective peptide Colivelin. Mol Neurobiol 2007;35(1):55-84 (Pubitemid 47010928)
4. Citron M, Westaway D, Xia W, et al. Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice. Nat Med 1997;3(1):67-72 (Pubitemid 27019143)
5. Citron M, Oltersdorf T, Haass C, et al. Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-protein production. Nature 1992;360(6405):672-674 (Pubitemid 23007680)
6. Borchelt DR, Thinakaran G, Eckman CB, et al. Familial Alzheimer's disease-linked presenilin 1 variants elevate Aβ1-42/1-40 ratio in vitro and in vivo. Neuron 1996;17(5):1005-1013 (Pubitemid 26424026)
7. Bennett DA, Schneider JA, Arvanitakis Z, et al. Neuropathology of older persons without cognitive impairment from two community-based studies. Neurology 2006;66(12):1837-1844 (Pubitemid 44049813)
8. Nicoll JA, Wilkinson D, Holmes C, et al. Neuropathology of human Alzheimer disease after immunization with amyloid-β peptide: a case report. Nat Med 2003;9(4):448-452 (Pubitemid 36460079)
9. Gilman S, Koller M, Black RS, et al. Clinical effects of Aβ immunization (AN1792) in patients with AD in an interrupted trial. Neurology 2005;64(9):1553-1562 (Pubitemid 40617691)
10. Hashimoto Y, Niikura T, Tajima H, et al. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Aβ. Proc Natl Acad Sci USA 2001;98(11):6336-6341 (Pubitemid 32488239)
11. Hashimoto Y, Niikura T, Ito Y, et al. Detailed characterization of neuroprotection by a rescue factor humanin against various Alzheimer's disease-relevant insults. J Neurosci 2001;21(23):9235-9245 (Pubitemid 33096867)
12. Mamiya T, Ukai M. [Gly14]-Humanin improved the learning and memory impairment induced by scopolamine in vivo. Br J Pharmacol 2001;134(8):1597-1599 (Pubitemid 34038091)
13. Krejcova G, Patocka J, Slaninova J. Effect of humanin analogues on experimentally induced impairment of patial memory in rats. J Pept Sci 2004;10(10):636-639 (Pubitemid 39409623)
14. Tajima H, Kawasumi M, Chiba T, et al. A humanin derivative, S14G-HN, prevents amyloid-β-induced memory impairment in mice. J Neurosci Res 2005;79(5):714-723 (Pubitemid 40476451)
15. Chiba T, Yamada M, Hashimoto Y, et al. Development of a femtomolar-acting humanin derivative named colivelin by attaching activity-dependent neurotrophic factor to its N terminus: characterization of colivelin-mediated neuroprotection against Alzheimer's disease-relevant insults in vitro and in vivo. J Neurosci 2005;25(44):10252-10261 (Pubitemid 41636222)
16. Tajima H, Niikura T, Hashimoto Y, et al. Evidence for in vivo production of Humanin peptide, a neuroprotective factor against Alzheimer's disease-related insults. Neurosci Lett 2002;324(3):227-231 (Pubitemid 34493875)
17. Caricasole A, Bruno V, Cappuccio I, et al. A novel rat gene encoding a Humanin-like peptide endowed with broad neuroprotective activity. FASEB J 2002;16(10):1331-1333
18. Bodzioch M, Lapicka-Bodzioch K, Zapala B, et al. Evidence for potential functionality of nuclearly-encoded humanin isoforms. Genomics 2009: published online 27 May 2009, doi:10.1016/j.ygeno.2009.05.006
19. Chiba T, Hashimoto Y, Tajima H, et al. Neuroprotective effect of activity-dependent neurotrophic factor against toxicity from familial amyotrophic lateral sclerosis-linked mutant SOD1 in vitro and in vivo. J Neurosci Res 2004;78(4):542-552 (Pubitemid 39536498)
20. Kunesova G, Hlavacek J, Patocka J, et al. The multiple T-maze in vivo testing of the neuroprotective effect of humanin analogues. Peptides 2008;29(11):1982-1987
21. Ying G, Iribarren P, Zhou Y, et al. Humanin, a newly identified neuroprotective factor, uses the G protein-coupled formylpeptide receptor-like-1 as a functional receptor. J Immunol 2004;172(11):7078-7085 (Pubitemid 38669150)
22. Guo B, Zhai D, Cabezas E, et al. Humanin peptide suppresses apoptosis by interfering with Bax activation. Nature 2003;423(6938):456-461 (Pubitemid 36626999)
23. Zhai D, Luciano F, Zhu X, et al. Humanin binds and nullifies Bid activity by blocking its activation of Bax and Bak. J Biol Chem 2005;280(16):15815-15824 (Pubitemid 40616702)
24. Luciano F, Zhai D, Zhu X, et al. Cytoprotective peptide humanin binds and inhibits proapoptotic Bcl-2/Bax family protein BimEL. J Biol Chem 2005;280(16):15825-15835 (Pubitemid 40616703)
25. Ikonen M, Liu B, Hashimoto Y, et al. Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis. Proc Natl Acad Sci USA 2003;100(22):13042-13047 (Pubitemid 37340022)
26. Hashimoto Y, Kurita M, Aiso S, et al. Humanin inhibits neuronal cell death by interacting with a cytokine receptor complex or complexes involving CNTF receptor α/WSX-1/gp130. Mol Biol Cell 2009;20(12):2864-2873
27. Hashimoto Y, Suzuki H, Aiso S, et al. Involvement of tyrosine kinases and STAT3 in Humanin-mediated neuroprotection. Life Sci 2005;77(24):3092-3104
28. Yamada M, Chiba T, Sasabe J, et al. Nasal Colivelin treatment ameliorates memory impairment related to Alzheimer's disease. Neuropsychopharmacology 2008;33(8):2020-2032 (Pubitemid 351832605)
29. Chiba T, Yamada M, Sasabe J, et al. Amyloid-β causes memory impairment by disturbing the JAK2/STAT3 axis in hippocampal neurons. Mol Psychiatry 2009;14(2):206-222
30. Yamada M, Chiba T, Sasabe J, et al. Implanted cannula-mediated repetitive administration of Aβ25-35 into the mouse cerebral ventricle effectively impairs spatial working memory. Behav Brain Res 2005;164(2):139-146 (Pubitemid 41337867)
31. Hsiao K, Chapman P, Nilsen S, et al. Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science 1996;274(5284):99- 102
32. Wang D, Li H, Yuan H, et al. Humanin delays apoptosis in K562 cells by downregulation of P38 MAP kinase. Apoptosis 2005;10(5):963-971 (Pubitemid 41285576)
33. Xu X, Chua CC, Gao J, et al. Humanin is a novel neuroprotective agent against stroke. Stroke 2006;37(10):2613-2619 (Pubitemid 44454687)
34. Xu X, Chua CC, Gao J, et al. Neuroprotective effect of humanin on cerebral ischemia/reperfusion injury is mediated by a PI3K/Akt pathway. Brain Res 2008;1227:12-18
35. Zhang W, Miao J, Hao J, et al. Protective effect of S14G-humanin against beta-amyloid induced LTP inhibition in mouse hippocampal slices. Peptides 2009;30(6):1197-1202
36. Stephanou A, Latchman DS. Opposing actions of STAT-1 and STAT-3. Growth Factors 2005;23(3):177-182
37. Gao Q, Mezei G, Nie Y, et al. Anorectic estrogen mimics leptin's effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals. Nat Med 2007;13(1):89-94 (Pubitemid 46067391)
38. Dicou E, Attoub S, Gressens P. Neuroprotective effects of leptin in vivo and in vitro. Neuroreport 2001;12(18):3947-3951 (Pubitemid 33152431)
39. Guo Z, Jiang H, Xu X, et al. Leptin-mediated cell survival signaling in hippocampal neurons mediated by JAK STAT3 and mitochondrial stabilization. J Biol Chem 2008;283(3):1754-1763
40. Kawasumi M, Chiba T, Yamada M, et al. Targeted introduction of V642I mutation in amyloid precursor protein gene causes functional abnormality resembling early stage of Alzheimer's disease in aged mice. Eur J Neurosci 2004;19(10):2826-2838 (Pubitemid 38746399)
41. Chui DH, Tanahashi H, Ozawa K, et al. Transgenic mice with Alzheimer presenilin 1 mutations show accelerated neurodegeneration without amyloid plaque formation. Nat Med 1999;5(5):560-564 (Pubitemid 29220216)
42. Alvarez A, Cacabelos R, Sanpedro C, et al. Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in Alzheimer disease. Neurobiol Aging 2007;28(4):533-536 (Pubitemid 46282207)
43. Barry SP, Townsend PA, McCormick J, et al. STAT3 deletion sensitizes cells to oxidative stress. Biochem Biophys Res Commun 2009;385(3):324-329
44. Harris ME, Hensley K, Butterfield DA, et al. Direct evidence of oxidative injury produced by the Alzheimer's β-amyloid peptide (1-40) in cultured hippocampal neurons. Exp Neurol 1995;131(2):193-202
45. Guo Q, Sopher BL, Furukawa K, et al. Alzheimer's presenilin mutation sensitizes neural cells to apoptosis induced by trophic factor withdrawal and amyloid β-peptide: involvement of calcium and oxyradicals. J Neurosci 1997;17(11):4212-4222 (Pubitemid 27220612)
46. Yatin SM, Varadarajan S, Link CD, Butterfield DA. In vitro and in vivo oxidative stress associated with Alzheimer's amyloid beta-peptide (1-42). Neurobiol Aging 1999;20(3):325-330
47. Bartus RT, Dean RL 3rd, Beer B, Lippa AS. The cholinergic hypothesis of geriatric memory dysfunction. Science 1982;217(4558):408-414
48. Berse B, Blusztajn JK. Coordinated up-regulation of choline acetyltransferase and vesicular acetylcholine transporter gene expression by the retinoic acid receptor alpha, cAMP, and leukemia inhibitory factor/ciliary neurotrophic factor signaling pathways in a murine septal cell line. J Biol Chem 1995;270(38):22101-22104
49. Cheema SS, Arumugam D, Murray SS, Bartlett PF. Leukemia inhibitory factor maintains choline acetyltransferase expression in vivo. Neuroreport 1998;9(3):363-366 (Pubitemid 28109188)
50. Walker CD, Long H, Williams S, Richard D. Long-lasting effects of elevated neonatal leptin on rat hippocampal function, synaptic proteins and NMDA receptor subunits. J Neurosci Res 2007;85(4):816-828 (Pubitemid 46426081)
51. Le Greves M, Zhou Q, Berg M, et al. Growth hormone replacement in hypophysectomized rats affects spatial performance and hippocampal levels of NMDA receptor subunit and PSD-95 gene transcript levels. Exp Brain Res 2006;173(2):267-273 (Pubitemid 44264890)
52. Mahmoud GS, Grover LM. Growth hormone enhances excitatory synaptic transmission in area CA1 of rat hippocampus. J Neurophysiol 2006;95(5):2962-2974
53. Kubota K, Inoue K, Hashimoto R, et al. Tumor necrosis factor receptor-associated protein 1 regulates cell adhesion and synaptic morphology via modulation of N-cadherin expression. J Neurochem 2009;110(2):496-508
54. Wen Y, Yu WH, Maloney B, et al. Transcriptional regulation of β-secretase by p25/cdk5 leads to enhanced amyloidogenic processing. Neuron 2008;57(5):680-690 (Pubitemid 351335351)
55. Anagnostaras SG, Murphy GG, Hamilton SE, et al. Selective cognitive dysfunction in acetylcholine M1 muscarinic receptor mutant mice. Nat Neurosci 2003;6(1):51-58 (Pubitemid 36026332)
56. Caccamo A, Oddo S, Billings LM, et al. M1 receptors play a central role in modulating AD-like pathology in transgenic mice. Neuron 2006;49(5):671-682 (Pubitemid 43290127)
57. Murata S, Usuda N, Okano A, et al. Occurrence of a transcription factor, signal transducer and activators of transcription 3 (Stat3):in the postsynaptic density of the rat brain. Brain Res Mol Brain Res 2000;78(1-2):80-90 (Pubitemid 30417488)
58. Shmuel M, Nodel-Berner E, Hyman T, et al. Caveolin 2 regulates endocytosis and trafficking of the M1 muscarinic receptor in MDCK epithelial cells. Mol Biol Cell 2007;18(5):1570-1585 (Pubitemid 46717541)
59. Jasmin JF, Mercier I, Hnasko R, et al. Lung remodeling and pulmonary hypertension after myocardial infarction: pathogenic role of reduced caveolin expression. Cardiovasc Res 2004;63(4):747-755 (Pubitemid 39078689)
60. Sur C, Mallorga PJ, Wittmann M, et al. N-desmethylclozapine, an allosteric agonist at muscarinic 1 receptor, potentiates N-methyl-D-aspartate receptor activity. Proc Natl Acad Sci USA 2003;100(23):13674-13679 (Pubitemid 37444798)
61. Meng Y, Zhang Y, Tregoubov V, et al. Abnormal spine morphology and enhanced LTP in LIMK-1 knockout mice. Neuron 2002;35(1):121-133 (Pubitemid 34804327)
62. Zervas M, Opitz T, Edelmann W, et al. Impaired hippocampal long-term potentiation in microtubule-associated protein 1B-deficient mice. J Neurosci Res 2005;82(1):83-92 (Pubitemid 41604800)
63. Brocke B, Lesch KP, Armbruster D, et al. Stathmin, a gene regulating neural plasticity, affects fear and anxiety processing in humans. Am J Med Genet B Neuropsychiatr Genet 2009: published online 12 June 2009, doi: 10.1002/ajmg.b.30989
64. Shumyatsky GP, Malleret G, Shin RM, et al. Stathmin, a gene enriched in the amygdala, controls both learned and innate fear. Cell 2005;123(4):697-709 (Pubitemid 41608470)
65. Sriram K, Benkovic SA, Hebert MA, et al. Induction of gp130-related cytokines and activation of JAK2/STAT3 pathway in astrocytes precedes up-regulation of glial fibrillary acidic protein in the 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine model of neurodegeneration: key signaling pathway for astrogliosis in vivo? J Biol Chem 2004;279(19):19936-19947
66. Satriotomo I, Bowen KK, Vemuganti R. JAK2 and STAT3 activation contributes to neuronal damage following transient focal cerebral ischemia. J Neurochem 2006;98(5):1353-1368 (Pubitemid 44200428)
67. Herrmann JE, Imura T, Song B, et al. STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury. J Neurosci 2008;28(28):7231-7243
68. Na YJ, Jin JK, Kim JI, et al. JAK-STAT signaling pathway mediates astrogliosis in brains of scrapie-infected mice. J Neurochem 2007;103(2):637-649
69. Suh HS, Kim MO, Lee SC. Inhibition of granulocyte-macrophage colony-stimulating factor signaling and microglial proliferation by anti-CD45RO: role of Hck tyrosine kinase and phosphatidylinositol 3-kinase/Akt. J Immunol 2005;174(5):2712-2719
70. Okada S, Nakamura M, Katoh H, et al. Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. Nat Med 2006;12(7):829-834 (Pubitemid 44050074)
71. Minegishi Y, Saito M, Tsuchiya S, et al. Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature 2007;448(7157):1058-1062 (Pubitemid 47345590)
72. Sano S, Chan KS, Carbajal S, et al. Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nat Med 2005;11(1):43-49 (Pubitemid 40215836)
73. Kishimoto T. Interleukin-6: from basic science to medicine-40 years in immunology. Annu Rev Immunol 2005;23:1-21 (Pubitemid 40563163)
74. Shouda T, Yoshida T, Hanada T, et al. Induction of the cytokine signal regulator SOCS3/CIS3 as a therapeutic strategy for treating inflammatory arthritis. J Clin Invest 2001;108(12):1781-1788 (Pubitemid 34015123)
75. Bromberg JF, Wrzeszczynska MH, Devgan G, et al. Stat3 as an oncogene. Cell 1999;98(3):295-303
76. Calo V, Migliavacca M, Bazan V, et al. STAT proteins: from normal control of cellular events to tumorigenesis. J Cell Physiol 2003;197(2):157-168 (Pubitemid 37485244)
77. Song JI, Grandis JR. STAT signaling in head and neck cancer. Oncogene 2000;19(21):2489-2495 (Pubitemid 30339204)
78. Nakashima K, Yanagisawa M, Arakawa H, et al. Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300. Science 1999;284(5413):479- 482 (Pubitemid 29289619)
79. Courtney C, Farrell D, Gray R, et al. Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000):randomised double-blind trial. Lancet 2004;363(9427):2105-2115
80. Howard RJ, Juszczak E, Ballard CG, et al. Donepezil for the treatment of agitation in Alzheimer's disease. N Engl J Med 2007;357(14):1382-1392 (Pubitemid 47535593)
81. Holmes C, Wilkinson D, Dean C, et al. The efficacy of donepezil in the treatment of neuropsychiatric symptoms in Alzheimer disease. Neurology 2004;63(2):214-219 (Pubitemid 38971117)
82. Tariot PN, Farlow MR, Grossberg GT, et al. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA 2004;291(3):317-324 (Pubitemid 38101604)
83. Available from: http://www.wyeth.com/irj/portal/news/archive?nav= display&navTo=/wyeth-html/home/news/pressreleases/2008/1217365320105.html
84. Eriksen JL, Sagi SA, Smith TE, et al. NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ42 in vivo. J Clin Invest 2003;112(3):440-449
85. Available from: http://investor.myriad.com/releasedetail.cfm?ReleaseID= 325471
86. Doody RS, Gavrilova SI, Sano M, et al. Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer's disease: a randomised, double-blind, placebo-controlled study. Lancet 2008;372(9634):207-215 (Pubitemid 351978110)
87. Thorne RG, Pronk GJ, Padmanabhan V, Frey WH 2nd. Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration. Neuroscience 2004;127(2):481-496
88. Gu ZJ, De Vos J, Rebouissou C, et al. Agonist anti-gp130 transducer monoclonal antibodies are human myeloma cell survival and growth factors. Leukemia 2000;14(1):188-197 (Pubitemid 30068391)