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作者(中文):黃銘豪
作者(外文):Huang, Ming-Hao
論文名稱(中文):The mechanism study of the knockdown of ribose-5-phosphate isomerase on polyglutamine toxicity attenuation in Drosophila melanogaster
論文名稱(外文):果蠅核醣-5-磷酸異構酶降低表現量對多麩醯胺酸蛋白毒性減緩作用機轉之研究
指導教授(中文):汪宏達
指導教授(外文):Wang, Horng-Dar
學位類別:碩士
校院名稱:國立清華大學
系所名稱:生物科技研究所
學號:9780580
出版年(民國):99
畢業學年度:98
語文別:英文
論文頁數:45
中文關鍵詞:果蠅多麩醯胺酸蛋白
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Neurodegenerative diseases are progressive loss of structure and function of neurons leading to neuronal cell death. Polyglutamine (polyQ) tract results from a repeat of CAG trinucleotide and causes irregular protein folding and degradation pathways and altered subcellular localization. The mutant polyQ can cause neurodegenerative diseases, including Huntington’s disease (HD). According to the previous studies, we found that the knockdown of ribose-5-phosphate isomerase (rpi) can rescue the defect fly eye from polyQ toxicity. However, the mechanism behind the effect is still unclear. In this thesis, I used Drosophila as a genetic model to approach this question and test some related possible factors involved in pentose phosphate pathway. In contrast with rpi act as convert ribulose-5-phosphate to ribose-5-phosphate, Ribose-5-phosphate epimerase (rpe) act as convert ribulose-5-phosphate to xylulose-5-phosphate. And protein phosphatase 2 A (PP2A) could be activated by xylulose-5-phosphate which is a intermediate product. I found that rpe and PP2A do not involve in rpi-knockdown mediated against polyQ toxicity. Glucose-6-phosphate dehydrogenase (G6PDH) maintains the reduced form of glutathione (GSH) against oxidative damage, yet it does not contribute to the rpi-knockdown mediated protect from polyQ toxicity. However, I found that knockdown of tansaldolase (tal) can revert back to the defect eye phenotype from the rescued eye by the rpi-knockdown-mediated attenuation of polyQ toxicity. The kncodown of rpi reduces the levels of phosphorylated S6K and 4EBP which are the downstream target proteins of TOR pathway. In sum, the knockdown of rpi on the rescued fly eye from polyQ toxicity may also depend on apoptosis, autophagy, and TOR pathways.
English abstract………………………………………………… Ⅰ
Chinese abstract…………………………………………………………… Ⅱ
Contents…………………………………………………………… Ⅲ
Introduction……………………………………………………… 1
Materials and methods………………………………………… 5
Results…………………………………………………………… 9
Discussion……………………………………………………… 17
Figures…………………………………………………………… 21
Tables…………………………………………………………… 35
References……………………………………………………… 38
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