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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 孔繁璐 | |
dc.contributor.author | Ya-Yun Lo | en |
dc.contributor.author | 羅雅云 | zh_TW |
dc.date.accessioned | 2021-06-07T23:52:49Z | - |
dc.date.copyright | 2014-02-25 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2013-11-22 | |
dc.identifier.citation | 1. Alzheimer, A., Uber eine eigenartige Erkrankung der Hirnrinde. Allgemeine Zeitschrift fur Psychiatrie und Psychisch-gerichtliche Medizin 1907, 64, 146-48.
2. Brookmeyer, R. S. C., Projections of Alzheimer's Disease in the United States and the Public Health Impact of Delaying Disease Onset. American Journal of Public Health 1998, 88 (9), 1337-1342. 3. Brookmeyer, R.; Johnson, E.; Ziegler-Graham, K.; Arrighi, H. M., Forecasting the global burden of Alzheimer’s disease. Alzheimer's and Dementia 2007, 3 (3), 186-191. 4. Williamson, J.; LaRusse, S., Genetics and genetic counseling: Recommendations for Alzheimer’s disease, frontotemporal dementia, and Creutzfeldt-Jakob disease. Current Neurology and Neuroscience Reports 2004, 4 (5), 351-357. 5. Wenk, G. L., Neuropathologic changes in Alzheimer's disease. The Journal of clinical psychiatry 2003, 64 Suppl 9, 7-10. 6. Selkoe, D. J., Biochemistry of altered brain proteins in Alzheimer's disease. Annual Review of Neuroscience 1989, 12, 463-90. 7. Kang, J.; Lemaire, H. G.; Unterbeck, A.; Salbaum, J. M.; Masters, C. L.; Grzeschik, K. H.; Multhaup, G.; Beyreuther, K.; Muller-Hill, B., The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 1987, 325 (6106), 733-6. 8. Kitaguchi, N.; Takahashi, Y.; Tokushima, Y.; Shiojiri, S.; Ito, H., Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity. Nature 1988, 331 (6156), 530-532. 9. Koo, E. H.; Sisodia, S. S.; Archer, D. R.; Martin, L. J.; Weidemann, A.; Beyreuther, K.; Fischer, P.; Masters, C. L.; Price, D. L., Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport. Proceedings of the National Academy of Sciences 1990, 87 (4), 1561-1565. 10. Mills, J.; Reiner, P. B., Regulation of amyloid precursor protein cleavage. Journal of Neurochemistry 1999, 72 (2), 443-60. 11. Golde, T. E.; Eckman, C. B.; Younkin, S. G., Biochemical detection of Abeta isoforms: implications for pathogenesis, diagnosis, and treatment of Alzheimer's disease. Biochimica et Biophysica Acta 2000, 1502 (1), 172-87. 12. Ponte, P.; Gonzalez-DeWhitt, P.; Schilling, J.; Miller, J.; Hsu, D.; Greenberg, B.; Davis, K.; Wallace, W.; Lieberburg, I.; Fuller, F., A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors. Nature 1988, 331 (6156), 525-7. 13. Tanzi, R. E.; McClatchey, A. I.; Lamperti, E. D.; Villa-Komaroff, L.; Gusella, J. F.; Neve, R. L., Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease. Nature 1988, 331 (6156), 528-30. 14. Kitaguchi, N.; Takahashi, Y.; Tokushima, Y.; Shiojiri, S.; Ito, H., Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity. Nature 1988, 331 (6156), 530-2. 15. Storey, E.; Cappai, R., The amyloid precursor protein of Alzheimer's disease and the Abeta peptide. Neuropathology and Applied Neurobiology 1999, 25 (2), 81-97. 16. Vetrivel, K. S.; Thinakaran, G., Amyloidogenic processing of beta-amyloid precursor protein in intracellular compartments. Neurology 2006, 66 (2 Suppl 1), S69-73. 17. O'Brien, R. J.; Wong, P. C., Amyloid precursor protein processing and Alzheimer's disease. Annual Review of Neuroscience 2011, 34 (1), 185-204. 18. Kokubo, H.; Saido, T. C.; Iwata, N.; Helms, J. B.; Shinohara, R.; Yamaguchi, H., Part of membrane-bound Abeta exists in rafts within senile plaques in Tg2576 mouse brain. Neurobiology of Aging 2005, 26 (4), 409-18. 19. Borg, J. P.; Ooi, J.; Levy, E.; Margolis, B., The phosphotyrosine interaction domains of X11 and FE65 bind to distinct sites on the YENPTY motif of amyloid precursor protein. Molecular and Cellular Biology 1996, 16 (11), 6229-41. 20. Tanzi, R. E.; Kovacs, D. M.; Kim, T. W.; Moir, R. D.; Guenette, S. Y.; Wasco, W., The gene defects responsible for familial Alzheimer's disease. Neurobiology of Disease 1996, 3 (3), 159-68. 21. Tanahashi, H.; Tabira, T., Genome structure and chromosomal mapping of the gene for Fe65L2 interacting with Alzheimer's beta-amyloid precursor protein. Biochemical and Biophysical Research Communications 1999, 258 (2), 385-9. 22. Chang, K. A.; Kim, H. S.; Ha, T. Y.; Ha, J. W.; Shin, K. Y.; Jeong, Y. H.; Lee, J. P.; Park, C. H.; Kim, S.; Baik, T. K.; Suh, Y. H., Phosphorylation of amyloid precursor protein (APP) at Thr668 regulates the nuclear translocation of the APP intracellular domain and induces neurodegeneration. Molecular and Cellular Biology 2006, 26 (11), 4327-38. 23. Ozaki, T.; Li, Y.; Kikuchi, H.; Tomita, T.; Iwatsubo, T.; Nakagawara, A., The intracellular domain of the amyloid precursor protein (AICD) enhances the p53-mediated apoptosis. Biochemical and Biophysical Research Communications 2006, 351 (1), 57-63. 24. Zheng, H.; Koo, E. H., The amyloid precursor protein: beyond amyloid. Molecular Neurodegeneration 2006, 1, 5. 25. Chen, T. Y.; Liu, P. H.; Ruan, C. T.; Chiu, L.; Kung, F. L., The intracellular domain of amyloid precursor protein interacts with flotillin-1, a lipid raft protein. Biochemical and Biophysical Research Communications 2006, 342 (1), 266-72. 26. Lee, M.-S.; Kao, S.-C.; Lemere, C. A.; Xia, W.; Tseng, H.-C.; Zhou, Y.; Neve, R.; Ahlijanian, M. K.; Tsai, L.-H., APP processing is regulated by cytoplasmic phosphorylation. The Journal of Cell Biology 2003, 163 (1), 83-95. 27. Iijima, K.-i.; Ando, K.; Takeda, S.; Satoh, Y.; Seki, T.; Itohara, S.; Greengard, P.; Kirino, Y.; Nairn, A. C.; Suzuki, T., Neuron-Specific Phosphorylation of Alzheimer's beta-Amyloid Precursor Protein by Cyclin-Dependent Kinase 5. Journal of Neurochemistry 2000, 75 (3), 1085-1091. 28. Oishi, M.; Nairn, A. C.; Czernik, A. J.; Lim, G. S.; Isohara, T.; Gandy, S. E.; Greengard, P.; Suzuki, T., The cytoplasmic domain of Alzheimer's amyloid precursor protein is phosphorylated at Thr654, Ser655, and Thr668 in adult rat brain and cultured cells. Molecular Medicine 1997, 3 (2), 111-23. 29. Aplin, A. E.; Gibb, G. M.; Jacobsen, J. S.; Gallo, J.-M.; Anderton, B. H., In Vitro Phosphorylation of the Cytoplasmic Domain of the Amyloid Precursor Protein by Glycogen Synthase Kinase-3beta. Journal of Neurochemistry 1996, 67 (2), 699-707. 30. Standen, C. L.; Brownlees, J.; Grierson, A. J.; Kesavapany, S.; Lau, K.-F.; McLoughlin, D. M.; Miller, C. C. J., Phosphorylation of thr668 in the cytoplasmic domain of the Alzheimer's disease amyloid precursor protein by stress-activated protein kinase 1b (Jun N-terminal kinase-3). Journal of Neurochemistry 2001, 76 (1), 316-320. 31. Iijima, K.; Ando, K.; Takeda, S.; Satoh, Y.; Seki, T.; Itohara, S.; Greengard, P.; Kirino, Y.; Nairn, A. C.; Suzuki, T., Neuron-specific phosphorylation of Alzheimer's beta-amyloid precursor protein by cyclin-dependent kinase 5. Journal of Neurochemistry 2000, 75 (3), 1085-91. 32. Ando, K.; Iijima, K. I.; Elliott, J. I.; Kirino, Y.; Suzuki, T., Phosphorylation-dependent regulation of the interaction of amyloid precursor protein with Fe65 affects the production of beta-amyloid. The Journal of Biological Chemistry 2001, 276 (43), 40353-61. 33. Ramelot, T. A.; Nicholson, L. K., Phosphorylation-induced structural changes in the amyloid precursor protein cytoplasmic tail detected by NMR. Journal of Molecular Biology 2001, 307 (3), 871-84. 34. Pastorino, L.; Sun, A.; Lu, P. J.; Zhou, X. Z.; Balastik, M.; Finn, G.; Wulf, G.; Lim, J.; Li, S. H.; Li, X.; Xia, W.; Nicholson, L. K.; Lu, K. P., The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-beta production. Nature 2006, 440 (7083), 528-34. 35. Sultana, R.; Boyd-Kimball, D.; Poon, H. F.; Cai, J.; Pierce, W. M.; Klein, J. B.; Markesbery, W. R.; Zhou, X. Z.; Lu, K. P.; Butterfield, D. A., Oxidative modification and down-regulation of Pin1 in Alzheimer's disease hippocampus: A redox proteomics analysis. Neurobiology of Aging 2006, 27 (7), 918-25. 36. Simons, K.; Ikonen, E., Functional rafts in cell membranes. Nature 1997, 387 (6633), 569-72. 37. Edidin, M., Lipids on the frontier: a century of cell-membrane bilayers. Nature Reviews Molecular Cell Biology 2003, 4 (5), 414-8. 38. Simons, K.; Toomre, D., Lipid rafts and signal transduction. Nature Reviews Molecular Cell Biology 2000, 1 (1), 31-9. 39. Kenworthy, A., Peering inside lipid rafts and caveolae. Trends in Biochemical Sciences 2002, 27 (9), 435-7. 40. Brown, D. A.; Rose, J. K., Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface. Cell 1992, 68 (3), 533-44. 41. Zisch, A. H.; D'Alessandri, L.; Amrein, K.; Ranscht, B.; Winterhalter, K. H.; Vaughan, L., The glypiated neuronal cell adhesion molecule contactin/F11 complexes with src-family protein tyrosine kinase Fyn. Molecular and Cellular Neuroscience 1995, 6 (3), 263-79. 42. Bickel, P. E.; Scherer, P. E.; Schnitzer, J. E.; Oh, P.; Lisanti, M. P.; Lodish, H. F., Flotillin and epidermal surface antigen define a new family of caveolae-associated integral membrane proteins. The Journal of Biological Chemistry 1997, 272 (21), 13793-802. 43. Hazarika, P.; Dham, N.; Patel, P.; Cho, M.; Weidner, D.; Goldsmith, L.; Duvic, M., Flotillin 2 is distinct from epidermal surface antigen (ESA) and is associated with filopodia formation. Journal of Cellular Biochemistry 1999, 75 (1), 147-59. 44. Malaga-Trillo, E.; Laessing, U.; Lang, D. M.; Meyer, A.; Stuermer, C. A., Evolution of duplicated reggie genes in zebrafish and goldfish. Journal of Molecular Evolution 2002, 54 (2), 235-45. 45. Rivera-Milla, E.; Stuermer, C. A.; Malaga-Trillo, E., Ancient origin of reggie (flotillin), reggie-like, and other lipid-raft proteins: convergent evolution of the SPFH domain. Cellular and Molecular Life Sciences 2006, 63 (3), 343-57. 46. Volonte, D.; Galbiati, F.; Li, S.; Nishiyama, K.; Okamoto, T.; Lisanti, M. P., Flotillins/cavatellins are differentially expressed in cells and tissues and form a hetero-oligomeric complex with caveolins in vivo. Characterization and epitope-mapping of a novel flotillin-1 monoclonal antibody probe. The Journal of Biological Chemistry 1999, 274 (18), 12702-9. 47. Edgar, A. J.; Polak, J. M., Flotillin-1: gene structure: cDNA cloning from human lung and the identification of alternative polyadenylation signals. The International Journal of Biochemistry & Cell Biology 2001, 33 (1), 53-64. 48. Rajendran, L.; Masilamani, M.; Solomon, S.; Tikkanen, R.; Stuermer, C. A. O.; Plattner, H.; Illges, H., Asymmetric localization of flotillins/reggies in preassembled platforms confers inherent polarity to hematopoietic cells. Proceedings of the National Academy of Sciences 2003, 100 (14), 8241-8246. 49. Galbiati, F.; Volonte, D.; Goltz, J. S.; Steele, Z.; Sen, J.; Jurcsak, J.; Stein, D.; Stevens, L.; Lisanti, M. P., Identification, sequence and developmental expression of invertebrate flotillins from Drosophila melanogaster. Gene 1998, 210 (2), 229-37. 50. Tavernarakis, N.; Driscoll, M.; Kyrpides, N. C., The SPFH domain: implicated in regulating targeted protein turnover in stomatins and other membrane-associated proteins. Trends in Biochemical Sciences 1999, 24 (11), 425-7. 51. Liu, J.; Deyoung, S. M.; Zhang, M.; Dold, L. H.; Saltiel, A. R., The stomatin/prohibitin/flotillin/HflK/C domain of flotillin-1 contains distinct sequences that direct plasma membrane localization and protein interactions in 3T3-L1 adipocytes. The Journal of Biological Chemistry 2005, 280 (16), 16125-34. 52. Babuke, T.; Ruonala, M.; Meister, M.; Amaddii, M.; Genzler, C.; Esposito, A.; Tikkanen, R., Hetero-oligomerization of reggie-1/flotillin-2 and reggie-2/flotillin-1 is required for their endocytosis. Cell Signal 2009, 21 (8), 1287-97. 53. Zhao, F.; Zhang, J.; Liu, Y. S.; Li, L.; He, Y. L., Research advances on flotillins. Virology Journal 2011, 8, 479. 54. Kokubo, H.; Lemere, C. A.; Yamaguchi, H., Localization of flotillins in human brain and their accumulation with the progression of Alzheimer's disease pathology. Neuroscience Letters 2000, 290 (2), 93-6. 55. Fassbender, K.; Simons, M.; Bergmann, C.; Stroick, M.; Lutjohann, D.; Keller, P.; Runz, H.; Kuhl, S.; Bertsch, T.; von Bergmann, K.; Hennerici, M.; Beyreuther, K.; Hartmann, T., Simvastatin strongly reduces levels of Alzheimer's disease beta -amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo. Proceedings of the National Academy of Sciences of the United States of America 2001, 98 (10), 5856-61. 56. Wahrle, S.; Das, P.; Nyborg, A. C.; McLendon, C.; Shoji, M.; Kawarabayashi, T.; Younkin, L. H.; Younkin, S. G.; Golde, T. E., Cholesterol-dependent gamma-secretase activity in buoyant cholesterol-rich membrane microdomains. Neurobiology of Disease 2002, 9 (1), 11-23. 57. Cordy, J. M.; Hussain, I.; Dingwall, C.; Hooper, N. M.; Turner, A. J., Exclusively targeting beta-secretase to lipid rafts by GPI-anchor addition up-regulates beta-site processing of the amyloid precursor protein. Proceedings of the National Academy of Sciences of the United States of America 2003, 100 (20), 11735-40. 58. Schneider, A.; Schulz-Schaeffer, W.; Hartmann, T.; Schulz, J. B.; Simons, M., Cholesterol depletion reduces aggregation of amyloid-beta peptide in hippocampal neurons. Neurobiology of Disease 2006, 23 (3), 573-7. 59. Urano, Y.; Hayashi, I.; Isoo, N.; Reid, P. C.; Shibasaki, Y.; Noguchi, N.; Tomita, T.; Iwatsubo, T.; Hamakubo, T.; Kodama, T., Association of active gamma-secretase complex with lipid rafts. The Journal of Lipid Research 2005, 46 (5), 904-12. 60. Frears, E. R.; Stephens, D. J.; Walters, C. E.; Davies, H.; Austen, B. M., The role of cholesterol in the biosynthesis of beta-amyloid. Neuroreport 1999, 10 (8), 1699-705. 61. Riddell, D. R.; Christie, G.; Hussain, I.; Dingwall, C., Compartmentalization of beta-secretase (Asp2) into low-buoyant density, noncaveolar lipid rafts. Current Biology 2001, 11 (16), 1288-93. 62. Girardot, N.; Allinquant, B.; Langui, D.; Laquerrière, A.; Dubois, B.; Hauw, J. J.; Duyckaerts, C., Accumulation of flotillin-1 in tangle-bearing neurones of Alzheimer's disease. Neuropathology and Applied Neurobiology 2003, 29 (5), 451-461. 63. Langui, D.; Girardot, N.; El Hachimi, K. H.; Allinquant, B.; Blanchard, V.; Pradier, L.; Duyckaerts, C., Subcellular Topography of Neuronal Aβ Peptide in APPxPS1 Transgenic Mice. The American Journal of Pathology 2004, 165 (5), 1465-1477. 64. Wolozin, B., Cholesterol and the biology of Alzheimer's disease. Neuron 2004, 41 (1), 7-10. 65. Wolfe, M. S.; Guénette, S. Y., APP at a glance. Journal of Cell Science 2007, 120 (18), 3157-3161. 66. Li, H.; Papadopoulos, V., Peripheral-type benzodiazepine receptor function in cholesterol transport. Identification of a putative cholesterol recognition/interaction amino acid sequence and consensus pattern. Endocrinology 1998, 139 (12), 4991-7. 67. Roitbak, T.; Surviladze, Z.; Tikkanen, R.; Wandinger-Ness, A., A polycystin multiprotein complex constitutes a cholesterol-containing signalling microdomain in human kidney epithelia. Biochemical Journal 2005, 392 (Pt 1), 29-38. 68. Gómez, V.; Sesé, M.; Santamaría, A.; Martínez, J. D.; Castellanos, E.; Soler, M.; Thomson, T. M.; Paciucci, R., Regulation of Aurora B Kinase by the Lipid Raft Protein Flotillin-1. Journal of Biological Chemistry 2010, 285 (27), 20683-20690. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17004 | - |
dc.description.abstract | 阿茲海默氏症 (Alzheimer’s disease) 是老年失智症中最常見的一種,經由病患腦組織切片可以發現有兩個主要的特徵,一是細胞內的神經纖維糾結(neurofibrillary tangles),另一則是細胞外老年斑 (senile plaques) 的形成。老年斑的主要成份是A-beta,A-beta的產生是類澱粉前驅蛋白 (amyloid precursor protein, APP) 經由連續性的酵素 (beta-secretase和gamma-secretase) 水解而形成。研究上認為有許多因素可能參與了APP的代謝,進而影響了A-beta的生成,像是脂筏 (lipid rafts)。由本實驗室之前的研究發現,一脂筏相關蛋白flotillin-1會與APP的C端片段 (APP intracellular domain, AICD) 產生交互作用,另外也發現APP的Thr668位置的磷酸化可能會影響了APP和flotillin-1之間的交互作用,進而改變了APP在細胞內的分佈及影響APP的代謝。因此我們想要找出APP與flotillin-1之間產生交互作用的重要區段,以及探討Thr668位置的磷酸化是否會影響了APP與flotillin-1之間的交互作用,除此之外,也要觀察此交互作用是否會影響APP的代謝,最後還要研究lipid rafts在APP代謝中所扮演的角色。研究結果是,經由石英晶體微天秤系統 (quartz crystal microbalance, QCM) 證實了flotillin-1160-185可與APP產生交互作用。利用模擬Thr668磷酸化 (APPT668E和AICDT668E) 及非磷酸化 (APPT668V和AICDT668A) 狀態的 mutants分別與flotillin-1進行交互作用的分析,APP的Thr668被磷酸化後會增進兩者間的交互作用能力,並可能藉由與flotillin-1之間的交互作用把APP帶到lipid rafts上,造成APP被beta-secretase及gamma-secretase水解,也就是APP代謝傾向走amyloidogenic pathway,使得A-beta生成量增加 (我們以C99/C83數值的變化來觀察)。經由siRNA knockdown實驗發現,當flotillin-1被knockdown時,APP代謝會傾向走non-amyloidogenic pathway,這證實flotillin-1對APP的proecessing有一定的作用。利用truncated flotillin-1 mutants去進行competition studies可以推出flotillin-1和APP間的交互作用會影響APP processing。總而言之,我們初步的結果指出flotillin-1可能會藉由與磷酸化APP的交互作用而促進APP代謝走向amyloidogenic pathway。 | zh_TW |
dc.description.abstract | Alzheimer's disease (AD) is the most common form of eldly dementia. It is characterized by two hallmarks in brain tissue slices of AD patients: one is intracellular neurofibrillary tangles (NFTs) and the other is extracellular senile plaques (SPs) formation. The main component of SPs is A-beta, which is generated by sequential proteolytic cleavages of amyloid precursor protein (APP) by beta- and gamma-secretases. Previous studies indicated that a number of factors, such as lipid rafts, may have been involved in APP processing, thereby affecting the A-beta production. Our earlier observations showed that AICD (APP intracellular domain) is able to interact with a lipid raft-associated protein, flotillin-1, and phosphorylation of APP at Thr668 probably affects the interaction between AICD and flotillin-1. It would change APP intracellular distribution and influence APP processing. Based on these studies, we want to identify regions of APP and flotillin-1 important for their interaction and to explore whether Thr668 phosphorylation can affect the interaction between APP and flotillin-1. In addition, we also want to see whether this interaction will affect the APP processing and to study the roles lipid rafts play in APP processing. Results from quartz crystal microbalance (QCM) studies indicated that APP can interact with flotillin-1160-185. Interaction studies using APPT668 mutants, APPT668E and T668A/V, which mimic constitutively phosphorylated and nonphosphorylated threonine, respectively, revealed that Thr668 phosphorylation will enhance the interaction between APP and flotillin-1, which in turn may promote APP translocation to lipid rafts, where it is subject to hydrolysis by beta-secretase and gamma-secretase to generate A-beta (as suggested by an increase in the C99/C83 ratio). According to siRNA knockdown studies, APP tends to be processed via the non-amyloidogenic pathway when flotillin-1 was knocked down. This result suggests that flotillin-1 may play a role in APP processing. Preliminary results from competition studies using truncated flotillin-1 mutants suggested APP processing may be modulated by APP-flotillin-1 interaction. In summary, our preliminary results suggest that flotillin-1 may promote amyloidogenic processing of APP through interacting with APP which is phosphorylated on Thr668. | en |
dc.description.provenance | Made available in DSpace on 2021-06-07T23:52:49Z (GMT). No. of bitstreams: 1 ntu-102-R99423010-1.pdf: 7264720 bytes, checksum: 84877cda6bc1df06d396e858b1818665 (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | 口試委員審定書............................................................................................................... i
致謝.................................................................................................................................. ii 中文摘要......................................................................................................................... iii 英文摘要……………………………………………………………………….……..... v 英文縮寫表………………………………………………………………………........ vii 目錄………………………………………………………………………...…………....x 序論…………………………………………………………………………...……...… 1 實驗目的……………………………………………………………………………...... 9 材料與方法………………………………………………………………………....…. 11 實驗結果……………………………………………………………………...…….…..29 一、 找出APP和flotillin-1上產生交互作用的重要區段……………...……... 29 二、 研究APP Thr668磷酸化在APP與flotillin-1交互作用中所扮演的角色...30 三、 觀察APP-flotillin-1的交互作用是否會影響APP的processing………....35 四、 利用flotillin-1 CRAC point mutants研究lipid rafts在APP processing中所扮演的角色…………...….…………………………………………….……38 討論…………………………………………………………………………………......41 圖表…………………………………………………………………………………......47 參考文獻…………………………………………………………………………..……62 | |
dc.language.iso | zh-TW | |
dc.title | 鑑定APP與flotillin-1之間產生交互作用的重要區段並探討此交互作用對APP processing的影響 | zh_TW |
dc.title | Identification of the regions mediating APP-flotillin-1 interaction and the effects of their interaction on APP processing | en |
dc.type | Thesis | |
dc.date.schoolyear | 102-1 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 許麗卿,顧記華 | |
dc.subject.keyword | 阿茲海默氏症,APP蛋白,Flotillin-1蛋白,lipid raft,Thr668磷酸化,C99/C83數值, | zh_TW |
dc.subject.keyword | Alzheimer’s disease,Amyloid precursor protein,Flotillin-1,lipid raft,Thr668 phosphorylation,C99/C83 ratio, | en |
dc.relation.page | 71 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2013-11-22 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 藥學研究所 | zh_TW |
顯示於系所單位: | 藥學系 |
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