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研究生:謝宗涵
研究生(外文):Tzung-Harn Hsieh
論文名稱:探討FKBP12對APP代謝過程的影響
論文名稱(外文):Investigation of the Potential Role of FKBP12 in APP Processing
指導教授:孔繁璐孔繁璐引用關係
指導教授(外文):Fan-Lu Kung
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:62
中文關鍵詞:阿茲海默症免疫親和素
外文關鍵詞:amyloid precursor proteinfkbp12
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前人研究發現AICD可以和一些chaperone產生交互作用;具有PPIase活性的Pin1即是其中一個例子,Pin1被認為參與APP之amyloidogenic代謝過程。之前的實驗利用酵母菌雙雜交及一系列生化方法發現發現另一個具有PPIase活性同時也是免疫親和素的FKBP12可以和AICD有交互作用;在HEK293T細胞中過量表現FKBP12顯示這種蛋白可能可以改變C99、C83的比例,而這個現象可以被免疫抑制劑FK506反轉。由於FK506的神經保護效果被認為可能跟FKBP52有關,我們也在HEK293T中過量表現FKBP52,初步實驗結果顯示FKBP12可以調控APP代謝過程,在模擬APPThr668位置被磷酸化的狀態下FKBP12可以加速使APP代謝過程趨向amyloidgenic pathway。而FKBP52雖然也能改變C83、C99的表現量,在APPThr668位置磷酸化的情形下也能加速反應,但卻是使APP代謝過程偏向non-amyloidogenic pathway,達到神經保護的效果,但上述之神經保護效果是否與FK506有關仍需進一步釐清。
Previous studies indicated some chaperones could interact with AICD, such as peptidyl-prolyl cis-trans isomerase (PPIase) Pin1. Pin1 has been reported to be involved in the amyloidogenic APP processing. Another PPIase FK506-binding protein 12 (also one of immunophilins) has been shown to interact with AICD via various biochemical approaches. Our results showed that overexpression of FKBP12 altered the ratio of C83 to C99 in HEK293T. Another FK506 binding protein 52 is also under investigation. Here we present FKBP12 may regulate APP processing; FKBP12 might accelerate APP undergo amyloidogenic pathway when APPThr668 was phosphorylated. However, FKBP52 might also alter the expression level of C83, C99, and their relative ratio, but it would accelerate APP undergo non-amyloidogenic pathway during the same conditions. FKBP52 showed neuroprotection ability, whether this effect was due to FK506 still under investigation.
致謝 …………………………………………………………………. ii
中文摘要 ……………………………………………………………. iii
英文摘要 ……………………………………………………………. iv
英文縮寫表 …………………………………………………………. v
序論 ……………….……………………………………………….. 1
1. Alzheimer’s disease ……………………………………… 1
2. FKBP12 (FK506 binding bprtein 12) ………………………… 6
3. APP與FKBP12 ………………………………………..…….. 9
研究目的 ………………………………………………………….... 11
材料與方法 ………………………………………………………… 12
1.實驗材料 …………………………………………………… 12
2.實驗方法 …………………………………………………… 13
實驗結果 …………………………………………………………… 21
討論 ………………………………………………………………… 29
圖表 ………………………………………………………………… 30
參考文獻 …………………………………………………………… 43
附錄 ………………………………………………………………… 58
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