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| 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.
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| 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 | |
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