請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/5408
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 廖永豐 | |
dc.contributor.author | Yung-Hao Tung | en |
dc.contributor.author | 童永豪 | zh_TW |
dc.date.accessioned | 2021-05-15T17:58:05Z | - |
dc.date.available | 2014-03-21 | |
dc.date.available | 2021-05-15T17:58:05Z | - |
dc.date.copyright | 2014-03-21 | |
dc.date.issued | 2014 | |
dc.date.submitted | 2014-02-27 | |
dc.identifier.citation | Alzheimer’s Association. 2008. 2008 Alzheimer’s disease facts and figures.
Alzheimer’s & Dementia 4. 110-133. Anderson JJ, Holtz G, Baskin PP, et al. 2005. Reductions in β-amyloid concentrations in vivo by the γ-secretase inhibitors BMS-289948 and BMS-299897. Biochem Pharmacol. 69(4):689–698. Anraku Y, Umemoto N, Hirata R, Ohya Y. 1992. Genetic and cell biological aspects of the yeast vacuolar H+-ATPase. J Bioenerg Biomembr. 24: 395–406. Artavanis-Tsakonas S, Rand MD, Lake RJ. 1999. Notch signaling: cell fate control and signal integration in development. Science. 284(5415):770-6. Bauerle C, Ho MN, Lindorfer MA, Stevens TH. 1993. The Saccharomyces cerevisiae VMA6 gene encodes the 36-kDa subunit of the vacuolar H+-ATPase membrane sector. J Biol Chem. 268:12749–12757. Busciglio J Gabuzda DH, Matsudaira P, Yankner BA. 1993. Generation of beta-amyloid in the secretory pathway in neuronal and nonneuronal cells. Proc Natl Acad Sci. 90: 2092–2096. Busciglio J, Pelsman A, Wong C, et al. 2002. Altered metabolism of the amyloid beta precursor protein is associated with mitochondrial dysfunction in Down’s syndrome. Neuron. 33:677-88. 25 Clague MJ, Urbe S, Aniento F, Gruenberg J. 1994. Vacuolar ATPase activity is required for endosomal carrier vesicle formation. J Biol Chem. 269: 21–24. DeStrooper B, Annaert W, Cupers P, et al. 1999. A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain. Nature. 398(6727): 518–522. Dries DR, Yu G. 2008. Assembly,maturation, and trafficking of the gamma-secretase complex in Alzheimer’s disease. Curr Alzheimer Res. 5: 132–146. Dries DR, Shah S, Han YH, Yu C, Yu S, Shearman MS, Yu G. 2009. GLU333 of nicastrin directly participates in gamma-secretase activity. J Biol Chem. 284: 29714– 29724. Duce JA, Tsatsanis A, Cater MA, James SA, Robb E, Wikhe K, Leong SL, Perez K, Johanssen T, Greenough MA, et al. 2010. Iron-export ferroxidase activity of β-amyloid precursor protein is inhibited by zinc in Alzheimer’s disease. Cell. 142: 857–867. Edbauer D, Winkler E, Regula JT, Pesold B, Steiner H, Haass C. 2003. Reconstitution of gamma-secretase activity. Nat Cell Biol. 5(5): 486-8. Faller P. 2009. Copper and zinc binding to amyloid-β: Coordination, dynamics, aggregation, reactivity and metalion transfer. Chembiochem. 10: 2837–2845. Forgac M. 2007. Vacuolar ATPases: rotary proton pumps in physiology and 26 pathophysiology. Nat Rev Mol Cell Biol. 8: 917–929. Fryer CJ, White JB, Jones KA. 2004. Mastermind recruits CyeC: CDK8 to phosphorylate the Notch ICD and coordinate activation with turnover. Mol Cell. 16: 509-20. Haapasaloa A, Kovacs DM. 2011. The Many Substrates of Presenilin/γ-Secretase. J Alzheimers Dis. 25(1): 3-28. Haass C, Selkoe DJ. 2007. Soluble protein oligomers in neurodegeneration: Lessons from the Alzheimer’s amyloid beta-peptide. Nat Rev Mol Cell Biol. 8: 101–112. Haass C, Koo EH, Mellon A, Hung AY, Selkoe DJ. 1992a. Targeting of cell-surface beta-amyloid precursor protein to lysosomes: Alternative processing into amyloidbearing fragments. Nature. 357: 500–503. Haass C, Scholssmacher M, Hung AY, Vigo-Pelfrey C, Mellon A, Ostaszewski B, Liederburg I, Koo F, Schenk D, Teplow D, et al. 1992b. Amyloid β-peptide is produced by cultured cells during normal metabolism. Nature. 359: 322–325. Hasegawa H, Sanjo N, Chen F, Gu YJ, Shier C, Petit A, Kawarai T, Katayama T, Schmidt SD, Mathews PM, et al. 2004. Both the sequence and length of the C terminus of PEN-2 are critical for intermolecular interactions and function of presenilin complexes. J Biol Chem. 279: 46455–46463. Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. 2003. Alzheimer disease in 27 the US population: prevalence estimates using the 2000 census. Arch Neurol. 60: 1119-22. Hemming ML, Elias JE, Gygi SP, Selkoe DJ. 2008. Proteomic profiling of g-secretase substrates and mapping of substrate requirements. PLoS Biol. 6: e257. Hirtz D, Thurman DJ, Gwinn-Hardy K, Mohamed M, Chaudhuri AR, Zalutsky R. 2007. How common are the “common” neurologic disorders? Neurology. 68: 326- 37. Iwata M, Imamura H, Stambouli E, Ikeda C, Tamakoshi M, Nagata K, Makyio H, Hankamer B, Barber J, Yoshida M, Yokoyama K, Iwata S. 2004. Crystal structure of a central stalk subunit C and reversible association/dissociation of vacuole-type ATPase. Proc Natl Acad Sci USA. 101: 59–64. Kaether C, Haass C, Steiner H. 2006. Assembly, trafficking and function of gamma-secretase. Neurodegener Dis. 3: 275–283. Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, Multhaup G, Beyreuther K, Muller-Hill B. 1987. The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature. 325: 733–736. Klionsky DJ, Nelson H, Nelson N. 1992. Compartment acidification is required for efficient sorting of proteins to the vacuole in Saccharomyces cerevisiae. J Biol Chem. 267: 3416–3422 Lai A, Sisodia SS, Trowbridge IS. 1995. Characterization of sorting signals in the 28 beta-amyloid precursor protein cytoplasmic domain. J Biol Chem. 270: 3565–3573. LaVoie MJ, Fraering PC, Ostaszewski BL, Ye W, Kimberly WT, Wolfe MS, Selkoe DJ. 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. Levitan D, Greenwald I. 1995. Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer’s disease gene. Nature. 377: 351–354. Li S, Hong S, Shepardson NE,Walsh DM, Shankar GM, Selkoe D. 2009. Soluble oligomers of amyloid b protein facilitate hippocampal long-term depression by disrupting neuronal glutamate uptake. Neuron. 62: 788–801. Louvi A, Artavanis-Tsakonas S. 2006. Notch signalling in vertebrate neural development. Nat Rev Neurosci. 7(2): 93-102. Lubman OY, Ilagan MX, Kopan R, Barrick D. 2007. Quantitative dissection of the Notch:CSL interaction: insights into the Notch-mediated transcriptional switch. J Mol Biol. 365: 577-89. Marquez-Sterling NR, Lo ACY, Sisodia SS, Koo EH. 1997. Trafficking of cell-surface beta-amyloid precursor protein: Evidence that a sorting intermediate participates in synaptic vesicle recycling. J Neurosci. 17: 140–151. McCarthy JV, Twomey C,Wujek P. 2009. Presenilin-dependent regulated intramembrane proteolysis and g-secretase activity. Cell Mol Life Sci. 66: 29 1534–1555. Moriyama Y, Madea M, Futai M. 1992. The role of V-ATPase in neuronal and endocrine systems. J Exp Biol. 172: 171–178. Nixon RA. 2007. Autophagy, amyloidogenesis and Alzheimer disease. J Cell Sci. 120: 4081–4091. Numoto N, Kita A, Miki K. 2004. Structure of the C subunit of V-type ATPase from Thermus thermophilus at 1.85 A resolution. Acta Crystallogr D Biol Crystallogr. 60: 810–815. Pasternak SH, Callahan JW, Mahuran DJ. 2004. The role of the endosomal/lysosomal system in amyloid-beta production and the pathophysiology of Alzheimer’s disease: Reexamining the spatial paradox from a lysosomal perspective. J Alzheimers Dis. 6: 53–65. Prokop S, Shirotani K, EdbauerD, Haass C, Steiner H. 2004. Requirement of PEN-2 for stabilization of the presenilin N-/C-terminal fragment heterodimer within the gamma-secretase complex. J Biol Chem. 279: 23255– 23261. Querfurth HW, LaFerla FM. 2010. Alzheimer’s Disease. N Engl J Med. 362: 329-44 Relini A, Cavalleri O, Rolandi R, Gliozzi A. 2009. The two fold aspect of the interplay of amyloidogenic proteins with lipid membranes. Chem Phys Lipids. 158: 1–9. Sahagian GG, Novikoff, PM. 1994. The Liver: Biology and Pathobiology (Arias I, 30 Boyer J, Fausto N, Jakoby W, Schachter D, Shafritz D, eds) 3rd Ed, 275–291. Raven Press, New York. Selkoe DJ. 2001. Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev. 81: 741-66. Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. 2011. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med. doi: 10.1101/cshperspect. a006189. Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H, Davis D, Sinha S, Schlossmacher M, Whaley J, Swindlehurst C, et al. 1992. Isolation and quantification of soluble Alzheimer’s beta-peptide from biological fluids. Nature. 359: 325–327. Shah S, Lee SF, Tabuchi K, Hao YH, Yu C, LaPlant Q, Ball H, Dann CE 3rd, Sudhof T, Yu G. 2005. Nicastrin functions as a gamma-secretase-substrate receptor. Cell. 122: 435– 447. Shankar GM, Bloodgood BL, Townsend M, Walsh DM, Selkoe DJ, Sabatini BL. 2007. Natural oligomers of the Alzheimer amyloid-b protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor- dependent signaling pathway. J Neurosci. 27: 2866– 2875. Smith AN, Borthwick KJ, Karet FE. 2002. Molecular cloning and characterization of novel tissue-specific isoforms of the human vacuolar H(+)-ATPase C, G and d 31 subunits, and their evaluation in autosomal recessive distal renal tubular acidosis. Gene. 297: 169–177. Smith AN, Richard WF, Sara LS, Fiona EK. 2008. The d subunit plays a central role in human vacuolar H+-ATPases. J Bioenerg Biomembr. 40: 371-383. Steiner H, Fluhrer R, Haass C. 2008. Intramembrane proteolysis by gamma-secretase. J Biol Chem. 283: 29627– 29631. Stevens TH, Forgac M. 1997. Structure, function and regulation of the vacuolar (H+)-ATPase. Annu Rev Cell Dev Biol. 13: 779–808. Tanzi RE, Bertram L. 2005. Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective. Cell. 120(4): 545-55. Thaker YR, Roessle M, Gruber G. 2007. The boxing glove shape of subunit d of the yeast V-ATPase in solution and the importance of disulfide formation for folding of this protein. J Bioenerg Biomembr. 39: 275–289. Thomas V, Serena D, Katia C, Carlo T, David B. 2010. The vacuolar ATPase in required for physilolgical as well as pathological activation of the Notch receptor. Development. 137: 1825-1832. Tsunematsu R, Nakayama K, Oike Y, Nishiyama M, Ishida N, Hatakeyama S, et al. Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascukar development. J Biol Chem. 2004: 279:9417-23. 32 Tsuyoshi N, Shoko KN, Forgac M. 2003. Expression and Function of the Mouse V-ATPase d Subunit Isoforms. J Biol Chem. 278: 46396-46402. Valapala M, Hose S, Gongora C, Dong L, Wawrousek E, Zigler JS Jr, Sinha D. 2013. Impaired endolysosomal function disrupts Notch signaling in optic nerve astrocytes. Nat Commun. 4: 1629. Wakabayashi T, Craessaerts K, Bammens L, Bentahir M, Borgions F, Herdewijn P, Staes A, Timmerman E, Vandekerckhove J, Rubinstein E, Boucheix C, Gevaert K, De Strooper B. 2009. Analysis of the gamma-secretase interactome and validation of its association with tetraspanin-enriched microdomains. Nat Cell Biol. 11: 1340-6. Weidemann A, Konig G, Bunke D, Fischer P, Salbaum JM, Masters CL, Beyreuther K. 1989. Identification, biogenesis, and localization of precursors of Alzheimer’s disease A4 amyloid protein. Cell. 57: 115–126. White JM. 1992. Membrane fusion. Science. 258: 917-924. Wolfe MS, Xia W, Ostaszewski BL, Diehl TS, Kimberly WT, Selkoe DJ. 1999. Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Nature. 398: 513–517. Wong GT, Manfra D, Poulet FM, Zhang Q, Josien H, Bara T, Engstrom L, Pinzon-Ortiz M, Fine JS, Lee HJ, et al. 2004. Chronic treatment with the g-secretase inhibitor 33 LY-411,575 inhibits b-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J Biol Chem. 279: 12876–12882. World Health Organization. Dementia: A Public Health Priority. Geneva: World Health Organization. 2012. Available from: http://whqlibdoc.who.int/publications/2012/9789241564458_eng.pdf. Accessed November 9, 2012. Yan Y, Natalie D, Trudi S. 2009. The vacuolar proton pump (V-ATPase) is required for Notch signaling and endosomal trafficking in Drosophila. Dev Cell. 17(3): 387–402. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/5408 | - |
dc.description.abstract | 阿茲海默症為全世界 65 歲以上老人失智症的主要原因,不斷增加的研究證據
指出了病人腦中,γ-seacretase 調控amyloid-β 的製造與此疾病之間有緊密關係,因 此一種治療或減緩病程的策略乃降低γ-seacretase 製造amyloid-β 之活性。近期研 究已發現了數個與γ-seacretase 具交互作用之蛋白質,具有調控γ-seacretase 活性之 能力。本實驗室先前的RNAi 篩選發現,囊泡型ATPase V0 的d1 次單元(ATP6V0d1) 為γ-seacretase 可能之調控者,為進一步明瞭此蛋白對γ-seacretase活性調控之角色, 因此在表現ATP6V0d1 之情況下,分別檢驗γ-seacretase 所催化之amyloid precursor protein (APP-C99)與Notch (NΔE)蛋白水解的反應。實驗結果結果顯示了表現 ATP6V0d1 對於γ-seacretase 所調控之NΔE 之水解具有顯著之增強現象,同時降低 了細胞內APP-C99 之表現量,此一發現顯示了ATP6V0d1 可能選擇性的影響了 γ-seacretase 與其受質的作用。 | zh_TW |
dc.description.abstract | Alzheimer’s disease (AD) is one of the major causes of dementia among people over
age of 65 around the world. Accumulated studies have shown a significant correlation between the AD pathogenesis and the γ-seacretase-mediated (Aβ) production in the patient’s brain. One of the possible strategies to cure or slow the disease progression of AD is to reduce γ-seacretase activity to lower Aβ production. Resent reports have found a number of γ-seacretase-interacting proteins that could potentially play a role in the modulation of γ-seacretase activity. Our RNAi screen identified one of the γ-seacretase-interacting proteins, vacuolar ATPase V0 domain d1 subunit (ATP6V0d1) as a possible γ-seacretase modulator. To validate its role in the modulation of γ-seacretase activity, γ-seacretase-catalyzed cleavages of amyloid precursor protein (APP-C99) and Notch (NΔE) were examined in response to the overexpression of ATP6V0d1. Our result demonstrated that overexpression of ATP6V0d1 does significantly enhance the γ-secretase-mediated cleavage of NΔE, and also markedly reduce the APP-C99 level. These findings suggest that ATP6V0d1 could act as a modulator by differentially governing the interactions between γ-secretase and its selective substrates. | en |
dc.description.provenance | Made available in DSpace on 2021-05-15T17:58:05Z (GMT). No. of bitstreams: 1 ntu-103-R00b41032-1.pdf: 2851335 bytes, checksum: e0329aa62bf5aa5ef4df3a66be478324 (MD5) Previous issue date: 2014 | en |
dc.description.tableofcontents | 致謝…………………………………………………………………………………i
中文摘要……………………………………………………………………………ii 英文摘要……………………………………………………………………………iii 緒論………………………………………………………………………………….1 實驗動機…………………………………………………………………………….7 研究材料…………………………………………………………………………….8 研究方法……………………………………………………………………………13 研究結果……………………………………………………………………………18 討論與結論…………………………………………………………………………20 參考資料……………………………………………………………………………24 | |
dc.language.iso | zh-TW | |
dc.title | 囊泡型 ATPase V0d1 次單元蛋白調節γ-Secretase 分
解類澱粉前驅蛋白與Notch 蛋白之反應 | zh_TW |
dc.title | The Differential Modulation of γ-Secretase-mediated
Cleavages of Amyloid Precursor Protein and Notch by the Vacuolar ATPase V0d1 Subunit | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 潘建源 | |
dc.contributor.oralexamcommittee | 陳俊宏 | |
dc.subject.keyword | 阿茲海默症,γ-seacretase,類澱粉前驅蛋白,Notch 路徑,囊泡型ATPase,溶小體,ATP6V0d1, | zh_TW |
dc.subject.keyword | Alzheimer’s disease,γ-seacretase,APP,Notch pathway,vacuolar ATPase,lysosome,ATP6V0d1, | en |
dc.relation.page | 43 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2014-02-27 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 動物學研究所 | zh_TW |
顯示於系所單位: | 動物學研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-103-1.pdf | 2.78 MB | Adobe PDF | 檢視/開啟 |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。