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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 廖永豐(Yung-Feng Liao) | |
| dc.contributor.author | Lan-Hsin Kuo | en |
| dc.contributor.author | 郭嵐忻 | zh_TW |
| dc.date.accessioned | 2021-06-13T03:18:45Z | - |
| dc.date.available | 2008-08-01 | |
| dc.date.copyright | 2006-08-01 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2006-07-28 | |
| dc.identifier.citation | Aggarwal, B. B. (2003). Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol 3, 745-756.
Akiyama, H., Barger, S., Barnum, S., Bradt, B., Bauer, J., Cole, G. M., Cooper, N. R., Eikelenboom, P., Emmerling, M., Fiebich, B. L., et al. (2000). Inflammation and Alzheimer's disease. Neurobiol Aging 21, 383-421. Anderson, A. J., Su, J. H., and Cotman, C. W. (1996). DNA damage and apoptosis in Alzheimer's disease: colocalization with c-Jun immunoreactivity, relationship to brain area, and effect of postmortem delay. J Neurosci 16, 1710-1719. Auron, P. E. (1998). The interleukin 1 receptor: ligand interactions and signal transduction. Cytokine Growth Factor Rev 9, 221-237. Bamberger, M. E., Harris, M. E., McDonald, D. R., Husemann, J., and Landreth, G. E. (2003). A cell surface receptor complex for fibrillar beta-amyloid mediates microglial activation. J Neurosci 23, 2665-2674. Barnes, P. J., and Karin, M. (1997). Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 336, 1066-1071. Baud, V., and Karin, M. (2001). Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol 11, 372-377. Baud, V., Liu, Z. G., Bennett, B., Suzuki, N., Xia, Y., and Karin, M. (1999). Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain. Genes Dev 13, 1297-1308. Baumann, K., Paganetti, P. A., Sturchler-Pierrat, C., Wong, C., Hartmann, H., Cescato, R., Frey, P., Yankner, B. A., Sommer, B., and Staufenbiel, M. (1997). Distinct processing of endogenous and overexpressed recombinant presenilin 1. Neurobiol Aging 18, 181-189. Bennett, B. L., Sasaki, D. T., Murray, B. W., O'Leary, E. C., Sakata, S. T., Xu, W., Leisten, J. C., Motiwala, A., Pierce, S., Satoh, Y., et al. (2001). SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc Natl Acad Sci U S A 98, 13681-13686. Blasko, I., Marx, F., Steiner, E., Hartmann, T., and Grubeck-Loebenstein, B. (1999). TNFalpha plus IFNgamma induce the production of Alzheimer beta-amyloid peptides and decrease the secretion of APPs. Faseb J 13, 63-68. Blasko, I., Veerhuis, R., Stampfer-Kountchev, M., Saurwein-Teissl, M., Eikelenboom, P., and Grubeck-Loebenstein, B. (2000). Costimulatory effects of interferon-gamma and interleukin-1beta or tumor necrosis factor alpha on the synthesis of Abeta1-40 and Abeta1-42 by human astrocytes. Neurobiol Dis 7, 682-689. Capell, A., Grunberg, J., Pesold, B., Diehlmann, A., Citron, M., Nixon, R., Beyreuther, K., Selkoe, D. J., and Haass, C. (1998). The proteolytic fragments of the Alzheimer's disease-associated presenilin-1 form heterodimers and occur as a 100-150-kDa molecular mass complex. J Biol Chem 273, 3205-3211. Carro, E., Trejo, J. L., Gomez-Isla, T., LeRoith, D., and Torres-Aleman, I. (2002). Serum insulin-like growth factor I regulates brain amyloid-beta levels. Nat Med 8, 1390-1397. Chang, L., and Karin, M. (2001). Mammalian MAP kinase signalling cascades. Nature 410, 37-40. Cirrito, J. R., and Holtzman, D. M. (2003). Amyloid beta and Alzheimer disease therapeutics: the devil may be in the details. J Clin Invest 112, 321-323. Combs, C. K., Karlo, J. C., Kao, S. C., and Landreth, G. E. (2001). beta-Amyloid stimulation of microglia and monocytes results in TNFalpha-dependent expression of inducible nitric oxide synthase and neuronal apoptosis. J Neurosci 21, 1179-1188. De Strooper, B., Annaert, W., Cupers, P., Saftig, P., Craessaerts, K., Mumm, J. S., Schroeter, E. H., Schrijvers, V., Wolfe, M. S., Ray, W. J., et al. (1999). A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398, 518-522. De Strooper, B., Beullens, M., Contreras, B., Levesque, L., Craessaerts, K., Cordell, B., Moechars, D., Bollen, M., Fraser, P., George-Hyslop, P. S., and Van Leuven, F. (1997). Phosphorylation, subcellular localization, and membrane orientation of the Alzheimer's disease-associated presenilins. J Biol Chem 272, 3590-3598. De Strooper, B., Saftig, P., Craessaerts, K., Vanderstichele, H., Guhde, G., Annaert, W., Von Figura, K., and Van Leuven, F. (1998). Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391, 387-390. Derijard, B., Raingeaud, J., Barrett, T., Wu, I. H., Han, J., Ulevitch, R. J., and Davis, R. J. (1995). Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms. Science 267, 682-685. Dickens, M., Rogers, J. S., Cavanagh, J., Raitano, A., Xia, Z., Halpern, J. R., Greenberg, M. E., Sawyers, C. L., and Davis, R. J. (1997). A cytoplasmic inhibitor of the JNK signal transduction pathway. Science 277, 693-696. Edbauer, D., Winkler, E., Regula, J. T., Pesold, B., Steiner, H., and Haass, C. (2003). Reconstitution of gamma-secretase activity. Nat Cell Biol 5, 486-488. Esler, W. P., and Wolfe, M. S. (2001). A portrait of Alzheimer secretases--new features and familiar faces. Science 293, 1449-1454. Evin, G., Canterford, L. D., Hoke, D. E., Sharples, R. A., Culvenor, J. G., and Masters, C. L. (2005). Transition-state analogue gamma-secretase inhibitors stabilize a 900 kDa presenilin/nicastrin complex. Biochemistry 44, 4332-4341. Fluhrer, R., Friedlein, A., Haass, C., and Walter, J. (2004). Phosphorylation of presenilin 1 at the caspase recognition site regulates its proteolytic processing and the progression of apoptosis. J Biol Chem 279, 1585-1593. Fraering, P. C., Ye, W., Strub, J. M., Dolios, G., LaVoie, M. J., Ostaszewski, B. L., van Dorsselaer, A., Wang, R., Selkoe, D. J., and Wolfe, M. S. (2004). Purification and characterization of the human gamma-secretase complex. Biochemistry 43, 9774-9789. Francis, R., McGrath, G., Zhang, J., Ruddy, D. A., Sym, M., Apfeld, J., Nicoll, M., Maxwell, M., Hai, B., Ellis, M. C., et al. (2002). aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation. Dev Cell 3, 85-97. Galcheva-Gargova, Z., Derijard, B., Wu, I. H., and Davis, R. J. (1994). An osmosensing signal transduction pathway in mammalian cells. Science 265, 806-808. Gianni, D., Zambrano, N., Bimonte, M., Minopoli, G., Mercken, L., Talamo, F., Scaloni, A., and Russo, T. (2003). Platelet-derived growth factor induces the beta-gamma-secretase-mediated cleavage of Alzheimer's amyloid precursor protein through a Src-Rac-dependent pathway. J Biol Chem 278, 9290-9297. Hanada, T., and Yoshimura, A. (2002). Regulation of cytokine signaling and inflammation. Cytokine Growth Factor Rev 13, 413-421. Henricson, A., Kall, L., and Sonnhammer, E. L. (2005). A novel transmembrane topology of presenilin based on reconciling experimental and computational evidence. Febs J 272, 2727-2733. Hoeflich, K. P., Yeh, W. C., Yao, Z., Mak, T. W., and Woodgett, J. R. (1999). Mediation of TNF receptor-associated factor effector functions by apoptosis signal-regulating kinase-1 (ASK1). Oncogene 18, 5814-5820. Huang, C., Ma, W. Y., Maxiner, A., Sun, Y., and Dong, Z. (1999). p38 kinase mediates UV-induced phosphorylation of p53 protein at serine 389. J Biol Chem 274, 12229-12235. in t' Veld, B. A., Ruitenberg, A., Hofman, A., Launer, L. J., van Duijn, C. M., Stijnen, T., Breteler, M. M., and Stricker, B. H. (2001). Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease. N Engl J Med 345, 1515-1521. Inomata, H., Nakamura, Y., Hayakawa, A., Takata, H., Suzuki, T., Miyazawa, K., and Kitamura, N. (2003). A scaffold protein JIP-1b enhances amyloid precursor protein phosphorylation by JNK and its association with kinesin light chain 1. J Biol Chem 278, 22946-22955. Janssens, S., and Beyaert, R. (2003). Functional diversity and regulation of different interleukin-1 receptor-associated kinase (IRAK) family members. Mol Cell 11, 293-302. Kao, S. C., Krichevsky, A. M., Kosik, K. S., and Tsai, L. H. (2004). BACE1 suppression by RNA interference in primary cortical neurons. J Biol Chem 279, 1942-1949. Kihiko, M. E., Tucker, H. M., Rydel, R. E., and Estus, S. (1999). c-Jun contributes to amyloid beta-induced neuronal apoptosis but is not necessary for amyloid beta-induced c-jun induction. J Neurochem 73, 2609-2612. Kim, J. W., Chang, T. S., Lee, J. E., Huh, S. H., Yeon, S. W., Yang, W. S., Joe, C. O., Mook-Jung, I., Tanzi, R. E., Kim, T. W., and Choi, E. J. (2001). Negative regulation of the SAPK/JNK signaling pathway by presenilin 1. J Cell Biol 153, 457-463. Kim, J. W., Kim, M. J., Kim, K. J., Yun, H. J., Chae, J. S., Hwang, S. G., Chang, T. S., Park, H. S., Lee, K. W., Han, P. L., et al. (2005). Notch interferes with the scaffold function of JNK-interacting protein 1 to inhibit the JNK signaling pathway. Proc Natl Acad Sci U S A 102, 14308-14313. Kimberly, W. T., LaVoie, M. J., Ostaszewski, B. L., Ye, W., Wolfe, M. S., and Selkoe, D. J. (2003). Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2. Proc Natl Acad Sci U S A 100, 6382-6387. Kirschenbaum, F., Hsu, S. C., Cordell, B., and McCarthy, J. V. (2001). Glycogen synthase kinase-3beta regulates presenilin 1 C-terminal fragment levels. J Biol Chem 276, 30701-30707. Kirschenbaum, F., Hsu, S. C., Cordell, B., and McCarthy, J. V. (2001). Substitution of a glycogen synthase kinase-3beta phosphorylation site in presenilin 1 separates presenilin function from beta-catenin signaling. J Biol Chem 276, 7366-7375. Kogel, D., Schomburg, R., Copanaki, E., and Prehn, J. H. (2005). Regulation of gene expression by the amyloid precursor protein: inhibition of the JNK/c-Jun pathway. Cell Death Differ 12, 1-9. Kyriakis, J. M., Banerjee, P., Nikolakaki, E., Dai, T., Rubie, E. A., Ahmad, M. F., Avruch, J., and Woodgett, J. R. (1994). The stress-activated protein kinase subfamily of c-Jun kinases. Nature 369, 156-160. Lau, K. F., Howlett, D. R., Kesavapany, S., Standen, C. L., Dingwall, C., McLoughlin, D. M., and Miller, C. C. (2002). Cyclin-dependent kinase-5/p35 phosphorylates Presenilin 1 to regulate carboxy-terminal fragment stability. Mol Cell Neurosci 20, 13-20. Laudon, H., Hansson, E. M., Melen, K., Bergman, A., Farmery, M. R., Winblad, B., Lendahl, U., von Heijne, G., and Naslund, J. (2005). A nine-transmembrane domain topology for presenilin 1. J Biol Chem 280, 35352-35360. LaVoie, M. J., Fraering, P. C., Ostaszewski, B. L., Ye, W., Kimberly, W. T., Wolfe, M. S., and Selkoe, D. J. (2003). Assembly of the gamma-secretase complex involves early formation of an intermediate subcomplex of Aph-1 and nicastrin. J Biol Chem 278, 37213-37222. Leicht, M., Marx, G., Karbach, D., Gekle, M., Kohler, T., and Zimmer, H. G. (2003). Mechanism of cell death of rat cardiac fibroblasts induced by serum depletion. Mol Cell Biochem 251, 119-126. Li, X., and Greenwald, I. (1998). Additional evidence for an eight-transmembrane-domain topology for Caenorhabditis elegans and human presenilins. Proc Natl Acad Sci U S A 95, 7109-7114. Liao, Y. F., Wang, B. J., Cheng, H. T., Kuo, L. H., and Wolfe, M. S. (2004). Tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma stimulate gamma-secretase-mediated cleavage of amyloid precursor protein through a JNK-dependent MAPK pathway. J Biol Chem 279, 49523-49532. Lim, G. P., Yang, F., Chu, T., Chen, P., Beech, W., Teter, B., Tran, T., Ubeda, O., Ashe, K. H., Frautschy, S. A., and Cole, G. M. (2000). Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease. J Neurosci 20, 5709-5714. Lim, G. P., Yang, F., Chu, T., Gahtan, E., Ubeda, O., Beech, W., Overmier, J. B., Hsiao-Ashec, K., Frautschy, S. A., and Cole, G. M. (2001). Ibuprofen effects on Alzheimer pathology and open field activity in APPsw transgenic mice. Neurobiol Aging 22, 983-991. MacGibbon, G. A., Lawlor, P. A., Walton, M., Sirimanne, E., Faull, R. L., Synek, B., Mee, E., Connor, B., and Dragunow, M. (1997). Expression of Fos, Jun, and Krox family proteins in Alzheimer's disease. Exp Neurol 147, 316-332. Matsuda, S., Matsuda, Y., and D'Adamio, L. (2003). Amyloid beta protein precursor (AbetaPP), but not AbetaPP-like protein 2, is bridged to the kinesin light chain by the scaffold protein JNK-interacting protein 1. J Biol Chem 278, 38601-38606. Matsuda, S., Yasukawa, T., Homma, Y., Ito, Y., Niikura, T., Hiraki, T., Hirai, S., Ohno, S., Kita, Y., Kawasumi, M., et al. (2001). c-Jun N-terminal kinase (JNK)-interacting protein-1b/islet-brain-1 scaffolds Alzheimer's amyloid precursor protein with JNK. J Neurosci 21, 6597-6607. McGeer, P. L., Schulzer, M., and McGeer, E. G. (1996). Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemiologic studies. Neurology 47, 425-432. Mercken, M., Takahashi, H., Honda, T., Sato, K., Murayama, M., Nakazato, Y., Noguchi, K., Imahori, K., and Takashima, A. (1996). Characterization of human presenilin 1 using N-terminal specific monoclonal antibodies: Evidence that Alzheimer mutations affect proteolytic processing. FEBS Lett 389, 297-303. Minden, A., Lin, A., McMahon, M., Lange-Carter, C., Derijard, B., Davis, R. J., Johnson, G. L., and Karin, M. (1994). Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK. Science 266, 1719-1723. Nishitoh, H., Saitoh, M., Mochida, Y., Takeda, K., Nakano, H., Rothe, M., Miyazono, K., and Ichijo, H. (1998). ASK1 is essential for JNK/SAPK activation by TRAF2. Mol Cell 2, 389-395. Ratovitski, T., Slunt, H. H., Thinakaran, G., Price, D. L., Sisodia, S. S., and Borchelt, D. R. (1997). Endoproteolytic processing and stabilization of wild-type and mutant presenilin. J Biol Chem 272, 24536-24541. Reynolds, C. H., Betts, J. C., Blackstock, W. P., Nebreda, A. R., and Anderton, B. H. (2000). Phosphorylation sites on tau identified by nanoelectrospray mass spectrometry: differences in vitro between the mitogen-activated protein kinases ERK2, c-Jun N-terminal kinase and P38, and glycogen synthase kinase-3beta. J Neurochem 74, 1587-1595. Reynolds, C. H., Utton, M. A., Gibb, G. M., Yates, A., and Anderton, B. H. (1997). Stress-activated protein kinase/c-jun N-terminal kinase phosphorylates tau protein. J Neurochem 68, 1736-1744. Rich, J. B., Rasmusson, D. X., Folstein, M. F., Carson, K. A., Kawas, C., and Brandt, J. (1995). Nonsteroidal anti-inflammatory drugs in Alzheimer's disease. Neurology 45, 51-55. Rogers, J., Kirby, L. C., Hempelman, S. R., Berry, D. L., McGeer, P. L., Kaszniak, A. W., Zalinski, J., Cofield, M., Mansukhani, L., Willson, P., and et al. (1993). Clinical trial of indomethacin in Alzheimer's disease. Neurology 43, 1609-1611. Scheinfeld, M. H., Roncarati, R., Vito, P., Lopez, P. A., Abdallah, M., and D'Adamio, L. (2002). Jun NH2-terminal kinase (JNK) interacting protein 1 (JIP1) binds the cytoplasmic domain of the Alzheimer's beta-amyloid precursor protein (APP). J Biol Chem 277, 3767-3775. Seeger, M., Nordstedt, C., Petanceska, S., Kovacs, D. M., Gouras, G. K., Hahne, S., Fraser, P., Levesque, L., Czernik, A. J., George-Hyslop, P. S., et al. (1997). Evidence for phosphorylation and oligomeric assembly of presenilin 1. Proc Natl Acad Sci U S A 94, 5090-5094. Selkoe, D. J. (2000). The genetics and molecular pathology of Alzheimer's disease: roles of amyloid and the presenilins. Neurol Clin 18, 903-922. Selkoe, D. J. (2001). Alzheimer's disease: genes, proteins, and therapy. Physiol Rev 81, 741-766. Shoji, M., Iwakami, N., Takeuchi, S., Waragai, M., Suzuki, M., Kanazawa, I., Lippa, C. F., Ono, S., and Okazawa, H. (2000). JNK activation is associated with intracellular beta-amyloid accumulation. Brain Res Mol Brain Res 85, 221-233. Sluss, H. K., Barrett, T., Derijard, B., and Davis, R. J. (1994). Signal transduction by tumor necrosis factor mediated by JNK protein kinases. Mol Cell Biol 14, 8376-8384. Steiner, H., Capell, A., Pesold, B., Citron, M., Kloetzel, P. M., Selkoe, D. J., Romig, H., Mendla, K., and Haass, C. (1998). Expression of Alzheimer's disease-associated presenilin-1 is controlled by proteolytic degradation and complex formation. J Biol Chem 273, 32322-32331. Stewart, W. F., Kawas, C., Corrada, M., and Metter, E. J. (1997). Risk of Alzheimer's disease and duration of NSAID use. Neurology 48, 626-632. Struhl, G., and Greenwald, I. (1999). Presenilin is required for activity and nuclear access of Notch in Drosophila. Nature 398, 522-525. Takasugi, N., Tomita, T., Hayashi, I., Tsuruoka, M., Niimura, M., Takahashi, Y., Thinakaran, G., and Iwatsubo, T. (2003). The role of presenilin cofactors in the gamma-secretase complex. Nature 422, 438-441. Tamagno, E., Bardini, P., Obbili, A., Vitali, A., Borghi, R., Zaccheo, D., Pronzato, M. A., Danni, O., Smith, M. A., Perry, G., and Tabaton, M. (2002). Oxidative stress increases expression and activity of BACE in NT2 neurons. Neurobiol Dis 10, 279-288. Tamagno, E., Parola, M., Bardini, P., Piccini, A., Borghi, R., Guglielmotto, M., Santoro, G., Davit, A., Danni, O., Smith, M. A., et al. (2005). Beta-site APP cleaving enzyme up-regulation induced by 4-hydroxynonenal is mediated by stress-activated protein kinases pathways. J Neurochem 92, 628-636. Tan, J., Town, T., Paris, D., Mori, T., Suo, Z., Crawford, F., Mattson, M. P., Flavell, R. A., and Mullan, M. (1999). Microglial activation resulting from CD40-CD40L interaction after beta-amyloid stimulation. Science 286, 2352-2355. Taru, H., Iijima, K., Hase, M., Kirino, Y., Yagi, Y., and Suzuki, T. (2002). Interaction of Alzheimer's beta -amyloid precursor family proteins with scaffold proteins of the JNK signaling cascade. J Biol Chem 277, 20070-20078. Thinakaran, G., Borchelt, D. R., Lee, M. K., Slunt, H. H., Spitzer, L., Kim, G., Ratovitsky, T., Davenport, F., Nordstedt, C., Seeger, M., et al. (1996). Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 17, 181-190. Tournier, C., Dong, C., Turner, T. K., Jones, S. N., Flavell, R. A., and Davis, R. J. (2001). MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines. Genes Dev 15, 1419-1426. Tournier, C., Whitmarsh, A. J., Cavanagh, J., Barrett, T., and Davis, R. J. (1999). The MKK7 gene encodes a group of c-Jun NH2-terminal kinase kinases. Mol Cell Biol 19, 1569-1581. Vassar, R., and Citron, M. (2000). Abeta-generating enzymes: recent advances in beta- and gamma-secretase research. Neuron 27, 419-422. Vingtdeux, V., Hamdane, M., Gompel, M., Begard, S., Drobecq, H., Ghestem, A., Grosjean, M. E., Kostanjevecki, V., Grognet, P., Vanmechelen, E., et al. (2005). Phosphorylation of amyloid precursor carboxy-terminal fragments enhances their processing by a gamma-secretase-dependent mechanism. Neurobiol Dis 20, 625-637. Walter, J., Grunberg, J., Capell, A., Pesold, B., Schindzielorz, A., Citron, M., Mendla, K., George-Hyslop, P. S., Multhaup, G., Selkoe, D. J., and Haass, C. (1997). Proteolytic processing of the Alzheimer disease-associated presenilin-1 generates an in vivo substrate for protein kinase C. Proc Natl Acad Sci U S A 94, 5349-5354. Walter, J., Grunberg, J., Schindzielorz, A., and Haass, C. (1998). Proteolytic fragments of the Alzheimer's disease associated presenilins-1 and -2 are phosphorylated in vivo by distinct cellular mechanisms. Biochemistry 37, 5961-5967. Weggen, S., Eriksen, J. L., Das, P., Sagi, S. A., Wang, R., Pietrzik, C. U., Findlay, K. A., Smith, T. E., Murphy, M. P., Bulter, T., et al. (2001). A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature 414, 212-216. Wei, Y., Yu, L., Bowen, J., Gorovsky, M. A., and Allis, C. D. (1999). Phosphorylation of histone H3 is required for proper chromosome condensation and segregation. Cell 97, 99-109. Whitmarsh, A. J., Cavanagh, J., Tournier, C., Yasuda, J., and Davis, R. J. (1998). A mammalian scaffold complex that selectively mediates MAP kinase activation. Science 281, 1671-1674. Wolfe, M. S., De Los Angeles, J., Miller, D. D., Xia, W., and Selkoe, D. J. (1999). Are presenilins intramembrane-cleaving proteases? Implications for the molecular mechanism of Alzheimer's disease. Biochemistry 38, 11223-11230. Wolfe, M. S., and Selkoe, D. J. (2002). Biochemistry. Intramembrane proteases--mixing oil and water. Science 296, 2156-2157. Wolfe, M. S., Xia, W., Ostaszewski, B. L., Diehl, T. S., Kimberly, W. T., and Selkoe, D. J. (1999). Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Nature 398, 513-517. Wyss-Coray, T., Lin, C., Yan, F., Yu, G. Q., Rohde, M., McConlogue, L., Masliah, E., and Mucke, L. (2001). TGF-beta1 promotes microglial amyloid-beta clearance and reduces plaque burden in transgenic mice. Nat Med 7, 612-618. Ye, Y., Lukinova, N., and Fortini, M. E. (1999). Neurogenic phenotypes and altered Notch processing in Drosophila Presenilin mutants. Nature 398, 525-529. Yu, G., Chen, F., Levesque, G., Nishimura, M., Zhang, D. M., Levesque, L., Rogaeva, E., Xu, D., Liang, Y., Duthie, M., et al. (1998). The presenilin 1 protein is a component of a high molecular weight intracellular complex that contains beta-catenin. J Biol Chem 273, 16470-16475. Zhu, X., Castellani, R. J., Takeda, A., Nunomura, A., Atwood, C. S., Perry, G., and Smith, M. A. (2001). Differential activation of neuronal ERK, JNK/SAPK and p38 in Alzheimer disease: the 'two hit' hypothesis. Mech Ageing Dev 123, 39-46. Zhu, X., Raina, A. K., Rottkamp, C. A., Aliev, G., Perry, G., Boux, H., and Smith, M. A. (2001). Activation and redistribution of c-jun N-terminal kinase/stress activated protein kinase in degenerating neurons in Alzheimer's disease. J Neurochem 76, 435-441. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/31733 | - |
| dc.description.abstract | Amyloid-β precursor protein (APP)經過β-secretase和γ-secretase相繼作用後產生Amyloid-β (Aβ)，是阿茲海默症致病機制中非常重要的一步。γ-secretase是負責在APP的transmembrane domain執行最後一步的蛋白水解反應，許多研究都認為這是阿茲海默症致病機制中最關鍵的ㄧ步。近來已有證據顯示γ-secretase為一個由presenilin (PS)、nicastrin (NCT)、Aph-1和Pen-2所組成的多蛋白複合體，且此四種蛋白的完善組合為其酵素活性的充要條件。先前的證據已指出一些cytokines能夠刺激γ-secretase的活性，其中又以tumer necrosis factor-α (TNF-α)最為有效。在最初的研究中，我們發現TNF-α透過JNK-dependent MAPK pathway活化γ-secretase，我們接著想看看cytokines對於γ-secretase的調控是否來自於JNK對於此蛋白水解酶的磷酸化所做的改變。為了提高對於γ-secretase磷酸化改變的解析度，我們建立了一細胞株大量表現有His-tag的NCT，以及正常的PS1、Aph-1、Pen-2和APP，因此可以用HIS-SelectedTM Cobalt Affinity Gel有效地純化整個γ-secretase複合體。在此，我們提出一些證據顯示TNF-α透過JNK促進PS1和NCT上的serine/threonine的磷酸化程度，同時活化γ-secretase；若用JNK的抑制劑─SP600125抑制JNK的活性，則會減低TNF-α對於PS1和NCT所引起的磷酸化。再者，活化的JNK能夠與γ-secretase一起被純化出來，並且活化的JNK可以在體外實驗中促進PS1和NCT的磷酸化。我們接著在PS1上找到一可能由JNK所調控的磷酸化位置，擁有此PS1突變的細胞表現出降低的γ-secretase活性。由我們的發現可以推論在TNF-α所引起γ-secretase的磷酸化中，JNK為其細胞中一重要的調停者，可能藉由直接與γ-secreatase相互作用來達到調控其鄰酸化程度與活性的目的。 | zh_TW |
| dc.description.abstract | Amyloid-β (Aβ), which is generated through β- and γ-secretase-mediated proteolysis of amyloid precursor protein (APP), plays a critical role in the pathogenesis of Alzheimer’s disease (AD). γ-Secretase which cleaves Amyloid-β precursor protein (APP) in its transmembrane domain catalyzes the final proteolytic step in the generation of Aβ. Recent evidence has demonstrated that γ-secretase is a multiprotein complex composed of presenilin (PS), nicastrin (NCT), Aph-1 and Pen-2 and that all four proteins are essential and sufficient for the proteolytic activity of γ-secretase. Previous evidence has shown that several cytokines can stimulate γ-secretase activity, and tumor necrosis factor-α (TNF-α) is the most potent one. In this study, we initially show that TNF-α activates γ-secretase via a JNK-dependent MAPK pathway. We then seek to determine whether this cytokine-elicited regulation of γ-secretase is due to alteration in the JNK-dependent phosphorylation of this protease. To improve the efficiency on visualizing the alteration in phosphorylation of γ-secretase, we have generated a CHO-derived cell line (γNCT-36) that stably co-expresses a His-tagged NCT along with PS1, Aph-1, Pen-2 and APP. The complexes of γ-secretase can then be efficiently pulled down by HIS-SelectedTM Cobalt Affinity Gel through the affinity of His-tagged NCT. Here, we present evidence that TNF-α elicits JNK-dependent serine/threonine phosphorylation of PS1 and NCT in γNCT-36 cells, concomitant with the stimulation of γ-secretase activity. Blocking JNK activity with a potent JNK inhibitor (SP600125) can reduce TNF-α-triggered phosphorylation of PS1 and NCT. Consistently, the activated JNK can be co-purified with γ-secretase complexes, and promotes the phosphorylation of PS1 and NCT in an in vitro kinase assay. A putative JNK-induced phosphorylation site of PS1 has been identified, and cells harboring this PS1 mutant exhibit decreased γ-secretase activity. Our findings suggest that JNK is an intracellular mediator of TNF-α-elicited phosphorylation of γ-secretase and may directly interact with γ-secretase to modulate its phosphorylation levels and hence its activity. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T03:18:45Z (GMT). No. of bitstreams: 1 ntu-95-R93b41004-1.pdf: 1639290 bytes, checksum: c0ed29ce1b2462a7a8154647e20bdf09 (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | 摘要 1
ABSTRACT 2 CONTENTS 4 APPENDIX OF TABLE 6 APPENDIX OF FIGURE 6 INTRODUCTION 7 MATERIAL AND METHODS 14 RESULT 22 DISCUSSION 30 REFERENCE 38 TABLE 51 FIGURE 52 | |
| dc.language.iso | en | |
| dc.subject | 老年癡呆症 | zh_TW |
| dc.subject | 阿茲海默氏症 | zh_TW |
| dc.subject | TNF-alpha | en |
| dc.subject | JNK | en |
| dc.subject | gamma-secretase | en |
| dc.title | TNF-α經由活化JNK MAPK pathway增強γ-secretase活性分子機制之研究 | zh_TW |
| dc.title | TNF-α enhances serine/threonine phosphorylation of γ-secretase via a JNK-dependent MAPK pathway | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳俊宏(Jiun-Hong Chen),黃偉邦(Wei-Pang Huang) | |
| dc.subject.keyword | 阿茲海默氏症,老年癡呆症, | zh_TW |
| dc.subject.keyword | gamma-secretase,JNK,TNF-alpha, | en |
| dc.relation.page | 65 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2006-07-30 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 動物學研究研究所 | zh_TW |
| Appears in Collections: | 動物學研究所 | |
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| File | Size | Format | |
|---|---|---|---|
| ntu-95-1.pdf Restricted Access | 1.6 MB | Adobe PDF |
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