| DC 欄位 |
值 |
語言 |
| DC.contributor | 化學學系 | zh_TW |
| DC.creator | 楊耀甄 | zh_TW |
| DC.creator | Yao-chen Yang | en_US |
| dc.date.accessioned | 2015-7-20T07:39:07Z | |
| dc.date.available | 2015-7-20T07:39:07Z | |
| dc.date.issued | 2015 | |
| dc.identifier.uri | http://ir.lib.ncu.edu.tw:88/thesis/view_etd.asp?URN=102223010 | |
| dc.contributor.department | 化學學系 | zh_TW |
| DC.description | 國立中央大學 | zh_TW |
| DC.description | National Central University | en_US |
| dc.description.abstract | 亨丁頓氏舞蹈症(Huntington’s disease, HD)是由於亨丁頓蛋白(Huntingtin)含有過多的麩醯胺酸(glutamine, Gln, Q)導致其聚集化形成大量的包涵體(inclusion body)累積。根據研究指出分子伴護蛋白除了一般認知上的幫助多肽鏈的摺疊，也會清除錯誤摺疊的蛋白質避免聚集化。其中，與核醣體相關的伴護蛋白──Trigger Factor(TF)，在原核生物界負責幫助大部分的新生成多肽鏈之摺疊。在本篇研究中我們利用生物物理化學的方法證明了TF在in vitro及in vivo的環境中確實會影響異常亨丁頓蛋白(mutant huntingtin, mHTT)的聚集化。首先我們運用GST-HTT polyQ蛋白系統探討TF對聚集化過程的影響，另外也以研究最為廣泛的DnaK伴護蛋白一起比較。由濾膜滯留分析法結果顯示TF及DnaK會使得mHTT的聚集物大量減少。透過穿透式電子顯微鏡觀察，mHTT的聚集化過程在TF與DnaK的存在下有所減緩。接著我們更進一步的以細胞實驗探討TF的作用。引人注目的是，於TF的存在下，mHTT的聚集物與寡聚物皆有減少的現象，且TF對神經突分化與細胞存活率有增加的作用。綜合實驗結果，我們發現TF的新作用──調控mHTT的聚集化及寡聚化過程，提供了對亨丁頓氏舞蹈症的治療方向。 | zh_TW |
| dc.description.abstract | The abundant accumulation of inclusion bodies containing polyglutamine (polyQ)-expanded mutant huntingtin (mHTT) aggregates is considered as the key pathological event in Huntington’s disease (HD). Literatures have reported that molecular chaperones participate in multiple cellular processes including assisting the folding of newly translated/damaged polypeptides and clearance of the misfolded proteins. Here, we show that Trigger factor (TF), a ribosome-associated chaperone responsible for facilitating the folding of nascent polypeptides in prokaryotes, is able to impact mHTT aggregation in vitro and in vivo.First, we applied GST-HTT polyQ protein system to explore the influence of TF and DnaK, a classical chaperone, in the aggregation process. Our result showed both TF and DnaK significantly reduced HTT(Q)43 aggregates as examined by filter retardation assay. Through transmission electron microscopy (TEM) observation, the mHTT aggregation process was retarded in the presence of TF similar as DnaK. We further examined the biological role of TF in mHTT-expressing N2A cells. Strikingly, we discovered mHTT oligomers were decreased in presence of TF. Furthermore, TF showed increased cell viability and neurite outgrowth in mHTT-expressing cells. Taken these together, we discovered a novel function of TF in modulating the oligomerization/aggregation process, which may benefit developments in HD therapeutic strategies in the future. | en_US |
| DC.subject | 亨丁頓氏舞蹈症 | zh_TW |
| DC.subject | 亨丁頓蛋白 | zh_TW |
| DC.subject | 蛋白質聚集化 | zh_TW |
| DC.subject | 蛋白質寡聚化 | zh_TW |
| DC.subject | 伴護蛋白 | zh_TW |
| DC.title | 伴護蛋白藉由抑制異常亨丁頓蛋白聚集化與寡聚化現象以引發良性效應 | zh_TW |
| dc.language.iso | zh-TW | zh-TW |
| DC.title | The suppression of aggregation/oligomerization process of mHTT protein by chaperones elicits beneficial effect | en_US |
| DC.type | 博碩士論文 | zh_TW |
| DC.type | thesis | en_US |
| DC.publisher | National Central University | en_US |