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Review

Agents targeting c-Jun N-terminal kinase pathway as potential neuroprotectants

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Pages 1373-1383 | Published online: 28 Oct 2005

Bibliography

  • CHANG L, KARIN M: Mammalian MAP signalling cascades. Nature (2001) 410(6824):37–40.
  • •This article reviews the organisation and physiological functions of MAPK cascades.
  • ICHIJO H: From receptors to stress-activated MAP kinases. Oncogene (1999) 18(45):6087–6093.
  • IRVING EA, BAMFORD M: Role of mitogen- and stress-activated kinases in ischemic injury. I Cereb. Blood Flow Metab. (2002) 22(6):631–647.
  • KYRIAKIS JM, AVRUCH J: Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev. (2001) 81(2)807–869.
  • DAVIS RJ: Signal transduction by the JNK group of MAP kinases. Cell (2000) 103(2):239–252.
  • TOURNIER C, WHITMARSH AJ, CAVANAGH J, BARRETT T, DAVIS RJ: Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase. Proc. Nati Acad. Li. USA (1997) 94(14):7337–7342.
  • ICHIJO H, NISHIDA E, IRIE K et al: Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science (1997) 275(5296):90–94.
  • KYRIAKIS JM, AVRUCH J: Protein kinase cascades activated by stress and inflammatory cytokines. Bioessays (1996) 18(7):567–577.
  • TIBBLES LA, ING YL, KIEFER F et al.: MLK-3 activates the SAPK/JNK and p38/ RK pathways via SEK1 and MKK3/6. Embo J. (1996) 15(24):7026–7035.
  • MINDEN A, LIN A, McMAHON M et al.: Differential activation of ERK and mitogen-activated protein kinases by Raf-1 and MEKK. Science (1994) 266(5191):1719–1723.
  • YAMAGUCHI K, SHIRAKABE K, SHIBUYA H et al.: Identification of a member of the MAPKKK family as a potential mediator of TGF-I3 signal transduction. Science (1995) 270(5244):2008–2011.
  • PAWSON T, SCOTT JD: Signaling through scaffold, anchoring, and adaptor proteins. Science (1997) 278(5346):2075–2080.
  • YASUDA J, WHITMARSH AJ, CAVANAGH J, SHARMA M, DAVIS RJ: The JIP group of mitogen-activated protein kinase scaffold proteins. Mol. Cell. Biol. (1999) 19(10):7245–7254.
  • HARDING TC, XUE L, BIENEMANN A et al.: Inhibition of JNK by overexpression of the JNL binding domain of JIP-1 prevents apoptosis in sympathetic neurons.. Chem. (2001) 276(7):4531–4534.
  • •This article reports that JBD expression Inhibits the phosphorylation of c-Jun and prevented apoptosis.
  • McDONALD PH, CHOW CW, WE et al.: 0-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3. Science (2000) 290(5496):1574–1577.
  • TAPON N, NAGATA K, LAMARCHE N, HALL A: A new rac target POSH is an 51-13-containing scaffold protein involved in the JNK and NF-KB signalling pathways. Embo J. (1998) 17(5):1395–1404.
  • XU Z, KUKEKOV NV, GREENE LA: POSH acts as a scaffold for a multiprotein complex that mediates JNK activation in apoptosis. Embo J. (2003) 22(2):252–261.
  • KUAN CY, YANG DD, ROY DR et al: The Jnkl and Jnk2 protein kinases are required for specific apoptosis during early development. Neuron (1999) 22(4):667–676.
  • ••Presents comprehensive evidence for thephysiological function of Jnk./ and -2genes In brain development.
  • XIA Z, DICKENS M, RAINGEAUD J, DAVIS RJ, GREENBERG ME: Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science (1995) 270(5240):1326–1331.
  • YANG DD, KUAN CY, AJ et al.: Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3gene. Nature (1997) 389(6653):865–870.
  • ••First observation shows that Jnk3-mediated signalling pathway is an important component in the pathogenesis of glutamate neurotoxicity.
  • BRUCKNER SR, TAMMARIELLO SP, KUAN CY et al: JNK3 contributes to c-Jun activation and apoptosis but not oxidative stress in nerve growth factor-deprived sympathetic neurons. J. Neurochem. (2001) 78(2):298–303.
  • SABAPATHY K, JO CHUM W, HOCHEDLINGER K et al.: Defective neural tube morphogenesis and altered apoptosis in the absence of both JNK1 and JNK2. Mech. Dev. (1999) 89(1-2):115–124.
  • BEHRENS A, SIBILIA M, WAGNER EF: Amino-terminal phosphorylation of c-Jun regulates stress-induced apoptosis and cellular proliferation. Nat. Genet. (1999) 21(3):326–329.
  • WHITMARSH AJ, KUAN CY, KENNEDY NJ et al.: Requirement of the JIP1 scaffold protein for stress-induced JNK activation. Genes Dev. (2001) 15(18):2421–2432.
  • IM JY, LEE KW, KIM MH et al: Repression of phospho-JNK and infarct volume in ischemic brain of JIPI-deficient mice. J. Neurosci. Res. (2003) 74(2):326–332.
  • SANCHEZ I, YUAN J: A convoluted way to die. Neuron (2001) 29(3):563–566.
  • LEI K, DAVIS RJ: JNK phosphorylation of Bim-related members of the Bc12 family induces Bax-dependent apoptosis. Proc. Natl. Acad. Sci. USA (2003) 100(5):2432–2437.
  • BOZYCZKO-COYNE D, O'KANE TM, WU ZL et al: CEP-1347/KT-7515, an inhibitor of SAPK/JNK pathway activation, promotes survival and blocks multiple events associated with AB-induced cortical neuron apoptosis. Neurochem. (2001) 77(3):849–863.
  • HARRIS CA, JOHNSON EM Jr: BH3-only Bcl-2 family members are coordinately regulated by the JNK pathway and require Bax to induce apoptosis in neurons. J. Biol. Chem. (2001) 276(40:37754–37760.
  • WHITFIELD J, NEAME SJ, PAQUET L, BERNARD 0, HAM J: Dominant-negative c-Jun promotes neuronal survival by reducing BIM expression and inhibiting mitochondrial cytochrome crelease. Neuron (2001) 29(3):629–643.
  • LE-NICULESCU H, BONFOCO E, KASUYA Y et al.: Withdrawal of survival factors results in activation of the JNK pathway in neuronal cells leading to Fas ligand induction and cell death.. Cell. Biol. (1999) 19(0:751–763.
  • SCHULZE-OSTHOFF K, FERRARI D, LOS M, WESSELBORG S, PETER ME: Apoptosis signaling by death receptors. Eur. Biochem. (1998) 254(3):439–459.
  • WATSON A, EILERS A, LALLEMAND D et al.: Phosphorylation of c-Jun is necessary for apoptosis induced by survival signal withdrawal in cerebellar granule neurons.. (1998) 18(2):751–762.
  • ADLER V, PINCUS MR, MINAMOTO T et al.: Conformation-dependent phosphorylation of p53. Proc. Natl. Acad. Sri. USA (1997) 94(5):1686–1691.
  • KYRIAKIS JM, AVRUCH J: Sounding the alarm: protein kinase cascades activated by stress and inflammation. J. Biol. Chem. (1996) 271(40):24313–24316.
  • DENG T, KARIN M: JunB differs from c-Jun in its DNA-binding and dimerization domains, and represses c-Jun by formation of inactive heterodimers. Genes Dev. (1993) 7(3):479–490.
  • GUPTA S, CAMPBELL D, DERIJARD B, DAVIS RJ: Transcription factor ATF2 regulation by the JNK signal transduction. Science (1995) 267(5196):389–393.
  • TSURUTA F, SUNAYAMA J, MORI Y et al: JNK promotes Bax translocation to mitochondria through phosphorylation of 14-3-3 proteins. Embo J. (2004) 23(8):1889–1899.
  • CHANG LK, PUTCHA GV, DESHMUKH M, JOHNSON EM Jr: Mitochondrial involvement in the point of no return in neuronal apoptosis. Biochimie (2002) 84(2-3):223–231.
  • WANG X: The expanding role of mitochondria in apoptosis. Genes Dev. (2001) 15(22):2922–2933.
  • CAIN K: Chemical-induced apoptosis: formation of the Apaf-1 apoptosome. Drug Meta& Rev (2003) 35(4):337–363.
  • CHEN J, NAGAYAMA T, JIN K et al: Induction of caspase-3-like protease may mediate delayed neuronal death in the hippocampus after transient cerebral ischemia. Neurosci. (1998) 18(13):4914–4928.
  • DLUZNIEWSKA J, BERESEWICZ M, WOJEWODZKA U, GAJKOWSKA B, ZABLOCKA B: Transient cerebral ischemia induces delayed proapoptotic Bad translocation to mitochondria in CA1 sector of hippocampus. Brain Res. Mol. Brain Res. (2005) 133(2):274–280.
  • MULLER GJ, STADELMANN C, BASTHOLM L et al.: Ischemia leads to apoptosis-and necrosis-like neuron death in the ischemic rat hippocampus. Brain Pathol. (2004) 14(4):415–424.
  • TOURNIER C, HESS P, YANG DD et al: Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. Science (2000) 288(5467):870–874.
  • FAN M, DU L, STONE AA, KM, CHAMBERS TC: Modulation of mitogen-activated protein kinases and phosphorylation of Bc1-2 by vinblastine represent persistent forms of normal fluctuations at G2-M1. Cancer Res. (2000) 60(22):6403–6407.
  • MIELKE K, HERDEGEN T: JNK and p38 stress kinases-degenerative effectors of signal-transduction-cascades in the nervous system. Prog. Neurobiol (2000) 61(0:45–60.
  • SCHROETER H, BOYD CS, AHMED R et al: c-Jun Nterminal kinase (JNK)-mediated modulation of brain mitochondria function: new target proteins JNK signalling in mitochondrion-dependent apoptosis. Biochem..1. (2003) 372\(Part 2):359–369.
  • CHAUHAN D, LI G, HIDESHIMA T et al.: JNK-dependent release of mitochondrial protein, Smac, during apoptosis in multiple myeloma (MM) cells. J. Biol. Chem. (2003) 278(20):17593–17596.
  • HARADA H, GRANT S: Apoptosis regulators. Rev. Clia Exp. Hematol (2003) 7(2):117–138.
  • ZHANG Q, ZHANG G, MENG F, TIAN H: Biphasic activation of apoptosis signal-regulating kinase 1-stress-activated protein kinase 1-c-Jun N-terminal protein kinase pathway is selectively mediated by Ca2'-permeable alpha-amino-3-hydroxy-5-methy1-4-isoxazolepropionate receptors involving oxidative stress following brain ischemia in rat hippocampus. Neurosci. Lett. (2003) 337(0:51–55.
  • ZHANG Q, ZHANG G: Activation and autophosphorylation of apoptosis signal-regulating kinase 1 (ASK 1) following cerebral ischemia in rat hippocampus. Neurosci. Lett. (2002) 329(2):232–236.
  • TIAN H, ZHANG Q, LI H, ZHANG G: Antioxidant N-acetylcysteine and AMPA/KA receptor antagonist DNQX inhibited mixed lineage kinase-3 activation following cerebral ischemia in rat hippocampus. Neurosci. Res. (2003) 47(1):47–53.
  • PEI DS, SUN YE GUAN QH et al: Postsynaptic density protein 95 antisense oligodeoxynucleotides inhibits the activation of MLK3 and JNK3 via the GluR6.PSD-95.MLK3 signaling module after transient cerebral ischemia in rat hippocampus. Neurosci. Lett. (2004) 367(1):71–75.
  • MIAO B, YIN XH, PEI DS, ZHANG QG, ZHANG GY: Neuroprotective effects of preconditioning ischemia on ischemic brain injury through down-regulating activation of JNK1/2 via N-methyl-D-aspartate receptor-mediated Akt1 activation. J. Biol. Chem. (2005) 280(23):21693–21699.
  • YIN XH, ZHANG QG, MIAO B, ZHANG GY: Neuroprotective effects of preconditioning ischaemia on ischaemic brain injury through inhibition of mixed-lineage kinase 3 via NMDA receptor-mediated Akt1 activation. J. Neurochem. (2005) 93(4):1021–1029.
  • GU Z, JIANG Q, ZHANG G: Extracellular signal-regulated kinase and c-Jun N-terminal protein kinase in ischemic tolerance. Neuroreport (2001) 12(16):3487–3491.
  • GU Z, JIANG Q, ZHANG G: c-Jun N-terminal kinase activation in hippocampal CA1 region was involved in ischemic injury. Neuroreport (2001) 12(5):897–900.
  • BERG MM, STERNBERG DW, PARADA LF, CHAO MV: K-252a inhibits nerve growth factor-induced trk proto-oncogene tyrosine phosphorylation and kinase activity. J. Biol. Chem. (1992) 267(1):13–16.
  • KANEKO M, SAITO Y, SAITO H et al: Neurotrophic 3,9-bisRalkylthio)methyll-and-bis(alkoxymethy0-K-252a derivatives. J. Med. Chem. (1997) 40(12):1863–1869.
  • GINGRICH DE, YANG SX, GW, ANGELES TS, HUDKINS RL: Synthesis, modeling, and in vitro activity of (3'S)-epi-K-252a analogues. Elucidating the stereochemical requirements of the 3'-sugar alcohol on trItA tyrosine kinase activity. J. Med. Chem. (2005) 48(11):3776–3783.
  • BORASIO GD: Differential effects of the protein kinase inhibitor K-252a on the in vitro survival of chick embryonic neurons. Neurosci. Lett. (1990) 108(1-2):207–212.
  • HASHIMOTO S, HAGINO A:-induced neurite outgrowth in PC12h cells. Exp. Cell Res. (1989) 184(2):351–359.
  • GLICKSMAN MA, PRANTNER JE, MEYER SL et al: K-252a and staurosporine promote choline acetyltransferase activity in rat spinal cord cultures. I Neurochem. (1993) 61(1):210–221.
  • GLICKSMAN MA, FORBES ME, PRANTNER JE, NEFF NT: K-252a promotes survival and choline acetyltransferase activity in striatal and basal forebrain neuronal cultures. J. Neurochem. (1995) 64(4):1502–1512.
  • ROUX PP, DORVAL G, BOUDREAU M et al: K252a and CEP1347 are neuroprotective compounds that inhibit mixed-lineage kinase-3 and induce activation of Akt and ERK. J. Biol. Chem. (2002) 277(51):49473–49480.
  • KNUSEL B, HEFTI F: K-252 compounds: modulators of neurotrophin signal transduction. I Neurochem. (1992) 59(6):1987–1996.
  • KNUSEL B, KAPLAN DR, JW et al.: K-252b selectively potentiates cellular actions and trk tyrosine phosphorylation mediated by neurotrophin-3. I Neurochem. (1992) 59(2):715–722.
  • MARONEY AC, GLICKSMAN MA, BASMA AN et al: Motoneuron apoptosis is blocked by CEP-1347 (KT 7515), a novel inhibitor of the JNK signaling pathway. J.Neurosci. (1998) 18(1):104–111.
  • ANGELES TS, YANG SX, STEFFLER C, DIONNE CA: Kinetics of trItA tyrosine kinase activity and inhibition by K-252a. Arch. Biochem. Biophys. (1998) 349(2):267–274.
  • SAPORITO MS, HUDKINS RL, MARONEY AC: Discovery of CEP-1347/ KT-7515, an inhibitor of the JNK/SAPK pathway for the treatment of neurodegenerative diseases.. Med. Chem. (2002) 40:23–62.
  • •A comprehensive review of-1347/KT-7515, with respect to its properties that make it a desirable clinical candidate for treatment of various neurodegenerative diseases.
  • MARONEY AC, FINN JP,-COYNE D et al: CEP-1347 (KT7515), an inhibitor of JNK activation, rescues sympathetic neurons and neuronally differentiated PC12 cells from death evoked by three distinct insults. I Neurochem. (1999) 73(5):1901–1912.
  • MARONEY AC, FINN JP, CONNORS TJ et al: Cep-1347 (KT7515), a semisynthetic inhibitor of the mixed lineage kinase family. Biol. Chem. (2001) 276(27):25302–25308.
  • HARRIS CA, DESHMUKH M, TSUI-PIERCHALA B, MARONEY AC, JOHNSON EM Jr: Inhibition of the c-Jun N-terminal kinase signaling pathway by the mixed lineage kinase inhibitor CEP-1347 (KT7515) preserves metabolism and growth of trophic factor-deprived neurons. J.Neurosci. (2002) 22(1):103–113.
  • BORASIO GD, HORSTMANN S, ANNESER JM, NEFF NT, MA: CEP-1347/KT7515, a JNK pathway inhibitor, supports the in vitro survival of chick embryonic neurons. Neuroreport (1998) 9(7):1435–1439.
  • MARONEY AC, LIPFERT L, FORBES ME et al: K-252a induces tyrosine phosphorylation of the focal adhesion kinase and neurite outgrowth in neuroblastoma SH-SY5Y cells.Neurochem. (1995) 64(2):540–549.
  • BOZYCZKO-COYNE D, MS, HUDKINS RL: Targeting the JNK pathway for therapeutic benefit in CNS disease. Curr. Drug Targets CNS Neurol Disord. (2002) 1(1):31–49.
  • ••Detailed review of how JNKs may beinvolved in the development of neuronal cell death and the progress on development of inhibitors targeting the JNK pathway for therapeutic benefit.
  • RESNICK L, FENNELL M: Targeting JNK3 for the treatment of neurodegenerative disorders. Discov. Today (2004) 9(21):932–939.
  • MANNING AM, DAVIS RJ: Targeting JNK for therapeutic benefit: from junk to gold? Nat. Rev Drug Discov. (2003) 2(7):554–565.
  • ••Excellent review summarising theapplication of JNK inhibitors in inflammatory, vascular, neurodegenerative, metabolic and oncological diseases in humans, and drug discovery targeting JNK.
  • WANG LH, BESIRLI CG, EM Jr: Mixed-lineage kinases: a target for the prevention of neurodegeneration. Ann. Rev Pharmacol Toxicol (2004) 44:451–474.
  • SAPORITO MS, THOMAS BA, SCOTT RW: MPTP activates c-Jun NH(2)-terminal kinase (JNK) and its upstream regulatory kinase MKK4 in nigrostriatal neurons in vivo. J. Neurochem. (2000) 75(3):1200–1208.
  • SAPORITO MS, BROWN EM, MS, CARSWELL S: CEP-1347/ KT-7515, an inhibitor of c-jun N-terminal kinase activation, attenuates the 1-methyl-4-phenyl tetrahydropyridine-mediated loss of nigrostriatal dopaminergic neurons in vivo. I Pharmacol Exp. Ther. (1999) 288(2):421–427.
  • SILVA RM, KUAN CY, RAKIC P, BURKE RE: Mixed lineage kinase-c-jun N-terminal kinase signaling pathway: a new therapeutic target in Parkinson's disease. Mov. Disord. (2005) 20(6):653–664.
  • PAN J, ZHANG QG, ZHANG GY: The neuroprotective effects of K252a through inhibiting MLK3/IVIKK7/JNK3 signaling pathway on ischemic brain injury in rat hippocampal CA1 region. Neuroscience (2005) 131(1):147–159.
  • HAN Z, BOYLE DL, CHANG L et al: c-Jun N-terminal kinase is required for expression and joint destruction in inflammatory arthritis. Clin. Invest. (2001) 108(1):73–81.
  • BENNETT BL, SASAKI DT, MURRAY BW et al: SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc. Natl. Acad. Sci. USA (2001) 98(24):13681–13686.
  • WANG W, MA C, MAO Z, LI M: JNK inhibition as a potential strategy in treating Parkinson's disease. Drug News Perspect. (2004) 17(10):646–654.
  • BOGOYEVITCH MA, BOEHM I, OAKLEY A, KETTERMAN AJ, RK: Targeting the JNK MAPK cascade for inhibition: basic science and therapeutic potential. Bloch/m. Biophys. Acta (2004) 1697(1-2):89–101.
  • BAIN J, McLAUCHLAN H, M, COHEN P: The specificities protein kinase inhibitors: an update. Biochem. J. (2003) 371\(Part 0:199–204.
  • GUAN QH, PEI DS, ZHANG QG et al: The neuroprotective action of SP600125, a new inhibitor of JNK, on transient brain ischemia/reperfusion-induced neuronal death in rat hippocampal CA1 via nuclear and non-nuclear pathways. Brain Res. (2005) 1035(1):51–59.
  • GAO Y, SIGNORE AP, YIN W et al.: Neuroprotection against focal ischemic brain injury by inhibition of c-Jun N-terminal kinase and attenuation of the mitochondrial apoptosis-signaling pathway. Cereb. Blood Flow Metab. (2005) 25(6):694–712.
  • WANG W, SHI L, XIE Y et al: SP600125, a new JNK inhibitor, protects dopaminergic neurons in the MPTP model of Parkinson's disease. Neurawi. Res. (2004) 48(2):195–202.
  • CARBONI S, HIVER A, SZYNDRALEWIEZ C et al: AS601245 (1,3-benzothiazol-2-y1 (2- [[2-(3-pyridinyl) ethyl] amino] -4 pyrimidinyl) acetonitrile): a c-Jun NH2-terminal protein kinase inhibitor with neuroprotective properties. Pharmacol. Exp. Ther. (2004) 310(0:25–32.
  • FERRANDI C, BALLERIO R, GAILLARD P et al.: Inhibition of c-Jun N-terminal kinase decreases cardiomyocyte apoptosis and infarct size after myocardial ischemia and reperfusion in anaesthetized rats. BE J. Pharmacol. (2004) 142(6):953–960.
  • CARBONI S, ANTONSSON B, GAILLARD P et al.: Control of death receptor and mitochondrial-dependent apoptosis by c-Jun N-terminal kinase in hippocampal CA1 neurones following global transient ischaemia. Neurochem. (2005) 92(5):1054–1060.
  • WHITMARSH AJ, CAVANAGH J, TOURNIER C, YASUDA J, DAVIS RJ: A mammalian scaffold complex that selectively mediates MAP kinase activation. Science (1998) 281(5383):1671–1674.
  • LEVCHENKO A, BRUCK J, PW: Scaffold proteins may biphasically affect the levels of mitogen-activated protein kinase signaling and reduce its threshold properties. Proc. Natl. Acad. Sci. USA (2000) 97(11):5818–5823.
  • BARR RK, KENDRICK TS, MA: Identification of the critical features of a small peptide inhibitor of JNK activity. J. Biol. Chem. (2002) 277(13):10987–10997.
  • SCHWARZE SR, HO A,-AKBANI A, DOWDY SF: In vivo protein transduction: delivery of a biologically active protein into the mouse. Science (1999) 285(5433):1569–1572.
  • JOLIOT A, PROCHIANTZ A: Transduction peptides: from technology to physiology. Nat. Cell Biol. (2004) 6(3):189–196.
  • BORSELLO T, CLARKE PG, HIRT L et al.: A peptide inhibitor of c-Jun N-terminal kinase protects against excitotoxicity and cerebral ischemia. Nat. Med. (2003) 9(9):1180–1186.
  • •A well-designed study evaluating an efficient experimental neuroprotective treatment against stroke.
  • HIRT L, BADAUT J, THEVENET J et al: D-JNKI1, a cell-penetrating c-Jun-N-terminal kinase inhibitor, protects against cell death in severe cerebral ischemia. Stroke (2004) 35(7):1738–1743.
  • WANG J, VAN DE WATER TR, BONNY C et al.: A peptide inhibitor of c-Jun N-terminal kinase protects against both aminoglycoside and acoustic trauma-induced auditory hair cell death and hearing loss. Neurosci. (2003) 23(24):8596–8607.
  • BONNY C, OBERSON A, NEGRI S, SAUSER C, SCHORDERET DF: Cell-permeable peptide inhibitors of JNK: novel blockers of 0-cell death. Diabetes (2001) 50(0:77–82.
  • NAWROT B: Targeting BACE with small inhibitory nucleic acids - a future for Alzheimer's disease therapy? Biochim. Pol. (2004) 51(2):431–444.
  • GOLDEN T, DEAN NM, RE: Use of antisense oligonucleotides: advantages, controls, and cardiovascular tissue. Microcirculation (2002) 9(0:51–64.
  • WEISS B, DAVIDKOVA G, ZHANG SP: Antisense strategies in neurobiology. Neurochem. Int. (1997) 31(3):321–348.
  • PROBST JC: Antisense and ribozyme design. Methods (2000) 22(3):271–281.
  • ZANKE BW, BOUDREAU K, RUBIE E et al.: The stress-activated protein kinase pathway mediates cell death following injury induced by cis-platinum, UV irradiation or heat. Curr. Biol. (1996) 6(5):606–613.
  • VERHEIJ M, BOSE R, LIN XH et al: Requirement for ceramide-initiated SAPK/ JNK signalling in stress-induced apoptosis. Nature (1996) 380(6569):75–79.
  • CHEN YR, WANG X, TEMPLETON D, DAVIS RJ, TAN TH: The role of c-Jun N-terminal kinase (INK) in apoptosis induced by ultraviolet C and gamma radiation. Duration of JNK activation may determine cell death and proliferation. J. Biol. Chem. (1996) 271(50):31929–31936.
  • PETERSON TC, PETERSON MR, ROBERTSON HA, DURING M, DRAGUNOW M: Selective down-regulation of clun gene expression by pentoxifylline and c-jun antisense interrupts platelet-derived growth factor signaling: pentoxifylline inhibits phosphorylation of c-Jun on serine 73. Mol. Pharmacol. (2002) 61(6):1476–1488.
  • KIM SD, MOON CK, EUN SY, RYU PD, JO SA: Identification of ASK1, MKK4, JNK, c-Jun, and caspase-3 as a signaling cascade involved in cadmium-induced neuronal cell apoptosis. Biochem. Biophys. Res. Commun. (2005) 328(1):326–334.
  • HASHIMOTO Y, NIIKURA T, CHIBA T et al.: The cytoplasmic domain of Alzheimer's amyloid-beta protein precursor causes sustained apoptosis signal-regulating kinase 1/c-Jun NH2-terminal kinase-mediated neurotoxic signal via dimerization. Pharmacol. Exp. Ther. (2003) 306(3):889–902.
  • YOSHIZUMI M, ABE J, TSUCHIYA K, BERK BC, TAMAKI T: Stress and vascular responses: atheroprotective effect of laminar fluid shear stress in endothelial cells: possible role of mitogen-activated protein kinases. Pharmacol. Sci. (2003) 91(3):172–176.
  • WAETZIG V, HERDEGEN T: A single c-Jun N-terminal kinase isoform (JNK3-p54) is an effector in both neuronal differentiation and cell death. Biol. Chem. (2003) 278(1):567–572.
  • CHANG L, JONES Y, ELLISMAN MH, GOLDSTEIN LS, KARIN M: JNK1 is required for maintenance of neuronal microtubules and controls phosphorylation of microtubule-associated proteins. Dev. Cell (2003) 4(4):521–533.
  • COFFEY ET, HONGISTO V, DICKENS M, DAVIS RJ, MJ: Dual roles for c-Jun N-terminal kinase in developmental and stress responses in cerebellar granule neurons. J. Neuracci. (2000) 20(20):7602–7613.
  • COFFEY ET, SMICIENE G, HONGISTO V et al.: c-Jun N-terminal protein kinase (JNK) 2/3 is specifically activated by stress, mediating c-Jun activation, in the presence of constitutive JNK1 activity in cerebellar neurons.. (2002) 22(11):4335–4345.
  • KENNEDY NJ, SLUSS HK, JONES SN et al.: Suppression of Ras-stimulated transformation by the JNK signal transduction pathway. Genes Dev. (2003) 17(5):629–637.
  • RAIVICH G, BOHATSCHEK M, DA COSTA C et al: The AP-1 transcription factor c-Jun is required for axonal regeneration. Neuron (2004) 43(1):57–67.
  • ENGELBERG D: Stress-activated protein kinases-tumor suppressors or tumor initiators? Semin. Cancer Biol. (2004) 14(4):271–282.
  • ••An excellent, comprehensive review of thebiology and pathology of the SAPKs, p38s and JNKs.

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