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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50724完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳振中(Jerry Chun Chung Chan) | |
| dc.contributor.author | Yu-Sheng Cheng | en |
| dc.contributor.author | 鄭友勝 | zh_TW |
| dc.date.accessioned | 2021-06-15T12:54:43Z | - |
| dc.date.available | 2019-07-26 | |
| dc.date.copyright | 2016-07-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-07-18 | |
| dc.identifier.citation | 第一章
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50724 | - |
| dc.description.abstract | Beta-amyloid peptides (Aβ)是用來研究阿茲海默症病徵的一個重要因素。現今，已經有很多文獻利用不同方法來了解Aβ 胜肽的聚合過程和結構樣貌。在Aβ 胜肽的聚合過程中，寡聚物被認為與單體和纖維相比，是神經毒性較高的物種。由於寡聚物具有多態性(polymorphism)，因此較難以研究寡聚物的結構樣貌。
在本實驗中，我們利用逆相微胞去模擬 Aβ 在擁擠的生物系統中寡聚化的 過程。利用Aerosol-OT (AOT, sodium bis(2-ethylexyl) sulfosuccinate)界面活性劑來製備逆相微胞系統，並選擇粒徑大小為33 nm(W0 為70)的逆相微胞來包覆單體，藉由逆相微胞碰撞性質，使其水相內的物質交換聚合而形成逆相微胞寡聚物(RM-Aβ oligomer)。利用ThT 螢光光譜和OMAB 斑點印跡法觀測Aβ 的聚合情形。我們也在不同培養天數下打破逆相微胞，並利用ThT 螢光監測25°C 静置培養下水相Aβ 的聚集情形，我們發現其聚集纖維的速度很快，是AOT 微胞促進纖維化，或是寡聚物作為一個核種(seed)，使聚合過程中所需跨越的能障較 低，而快速聚合成纖維，這點仍有待更進一步的實驗證實。 | zh_TW |
| dc.description.abstract | Beta-amyloid peptides (Aβ) are widely considered as the key factor in the investigation of Alzheimer's disease (AD). The formation and accumulation of the peptides have been studied for a long time. According to recent research, Aβ oligomers may be a more relevant therapeutic target than other species such as fibrillar aggregates.
To understand the process of Aβ oligomerization in this study, we employ reverse micelles (RMs) to simulate the crowded biological environment, in which the structure and kinetics of Aβ are studied. In water-in-oil microemulsion, water droplets are dispersed in isooctane surrounded by anionic surfactant, Aerosol-OT (AOT, sodium bis(2-ethylexyl) sulfosuccinate). The size of RM is related to water loading (W0) parameter, which is the ratio of water molecules to surfactant molecules (W0 = [H2O] / [surfactant]). We encapsulate Aβ in RMs (W0 = 70) with 33 nm in hydrodynamic diameter measured by dynamic light scattering. To monitor and analyze the structural properties of Aβ, we use the OMAB dot blot and fluorescent dye Thioflavin-T (ThT) which is a powerful tool for detecting amyloid peptide aggregation. Reverse micelles provide a confined space for the studies of the aggregation state of peptides. In addition, we also disrupt the reverse micelle in different incubation periods and use ThT fluorescence to keep track Aβ of incubating quiescently in water phase at 25°C. We find that it becomes into fibril quickly. However, further investigation are needed to understand either AOT micelles or oligomeric seeds promote aggregation. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T12:54:43Z (GMT). No. of bitstreams: 1 ntu-105-R03223143-1.pdf: 6550600 bytes, checksum: 4c25850abc454406c7c37bee9cd89697 (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 第1章 緒論 1
1-1 Aβ胜肽與阿茲海默症之關聯性 1 1-2 Aβ胜肽聚集過程-結構多樣性探討 5 1-3 Aβ寡聚物(oligomers) 8 1-3-1 寡聚物的特性和其種類 9 1-3-2 穩定寡聚物 14 1-4 逆相微胞簡介與製備方法 18 1-4-1 逆相微胞(Reverse micelle, RM)的組成 18 1-4-2 利用逆相微胞包覆蛋白 20 1-5 研究動機 22 1-6 參考資料 23 第2章 合成與鑑定 34 2-1 化學試劑與使用儀器 34 2-2 胜肽製備 38 2-2-1 胜肽合成 38 2-2-1 胜肽純化 39 2-2-3 胜肽鑑定 40 2-2-4 胜肽定量 43 2-3 包覆Aβ1-40單體之逆相微胞製備 45 2-3-1 Aβ1-40單體製備 45 2-3-3 選擇適當的逆相微胞系統 45 2-3-4 RM-Aβ的製備-直接注入法 47 2-3-5 反向萃取回Aβ胜肽 48 2-4 Aβ胜肽寡聚物、纖維及逆相微胞之鑑定方法 49 2-4-1 Thioflavin T (ThT) 螢光光譜 49 2-4-2 穿透式電子顯微鏡 52 2-4-3 動態光散射粒徑分析儀 54 2-4-4 傅里葉轉換紅外光譜(Fourier Transform Infrared, FTIR) 56 2-4-5 圓偏光二色光譜(Circular Dichroism, CD) 58 2-4-6 粒徑篩層析儀(Size Exclusion Chromatography, SEC) 59 2-4-7 斑點印跡法(Dot Blot) 60 2-6 參考文獻 61 第3章 實驗結果與討論 68 3-1 胜肽的合成、純化與鑑定 68 3-2 以逆相微胞包覆Aβ1-40胜肽單體 71 3-2-1 Aβ1-40胜肽單體製備 71 3-2-2 監控Aβ在逆相微胞的聚合情形 72 3-2-3 比較不同方法培養RM-Aβ 75 3-3 逆相微胞寡聚物的鑑定 77 3-4 結果討論 79 3-5 參考文獻 80 第4章 結論及未來展望 83 4-1論文總結 83 4-2未來展望 83 附錄A 84 不同培養條件下，Aβ1-40類澱粉樣纖維和寡聚物之鑑定 84 附錄B 87 逆相微胞系統 87 (一) 影響逆相微胞形成的因子 87 (二) 優化逆相微胞系統 91 附錄C 95 AOT微胞干擾ThT訊號 95 附錄D 97 移除AOT界面活性劑的方法 97 (1) SDS-Out™ Precipitation Kit1 97 (2) Pierce® Detergent Removal Spin Columns2 97 (3) Compat-Able™ Protein Assay Preparation Reagent Set3 98 (4) Bio-Beads® SM Hydrophobic and Polar Interaction Adsorbents4 98 附錄E 103 其他方法監控RM-Aβ的聚合情形 103 (1) SEC 103 (2) FTIR 104 (3) CD 105 附錄F 106 (一) 培養不同天數取出後的RM-Aβ 106 (二) 限制空間對Aβ聚合的影響 109 | |
| dc.language.iso | zh-TW | |
| dc.subject | 阿茲海默症 | zh_TW |
| dc.subject | 類澱粉多?分子 | zh_TW |
| dc.subject | 逆相微胞 | zh_TW |
| dc.subject | 阿茲海默症 | zh_TW |
| dc.subject | 類澱粉多?分子 | zh_TW |
| dc.subject | 逆相微胞 | zh_TW |
| dc.subject | AOT | en |
| dc.subject | RMs | en |
| dc.subject | Reverse micelles | en |
| dc.subject | AOT | en |
| dc.subject | Aerosol-OT | en |
| dc.subject | Aβ | en |
| dc.subject | beta-amyloid | en |
| dc.subject | AD | en |
| dc.subject | ThT | en |
| dc.subject | Thioflavin-T | en |
| dc.subject | ThT | en |
| dc.subject | Thioflavin-T | en |
| dc.subject | RMs | en |
| dc.subject | Reverse micelles | en |
| dc.subject | AD | en |
| dc.subject | beta-amyloid | en |
| dc.subject | Aβ | en |
| dc.subject | Aerosol-OT | en |
| dc.title | 以逆相微胞製備類澱粉多肽分子寡聚物之研究 | zh_TW |
| dc.title | Oligomeric aggregates of beta-amyloid peptides
confined in reverse micelles | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 戴桓青(Hwan-Ching Tai),黃人則(Joseph Jen-Tse Huang) | |
| dc.subject.keyword | 阿茲海默症,類澱粉多?分子,逆相微胞, | zh_TW |
| dc.subject.keyword | AD,beta-amyloid,Aβ,Aerosol-OT,AOT,Reverse micelles,RMs,Thioflavin-T,ThT, | en |
| dc.relation.page | 109 | |
| dc.identifier.doi | 10.6342/NTU201600752 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-07-18 | |
| dc.contributor.author-college | 理學院 | zh_TW |
| dc.contributor.author-dept | 化學研究所 | zh_TW |
| 顯示於系所單位： | 化學系 | |
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