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系統識別號 U0026-0812200911434124
論文名稱(中文) 貝它糊蛋白有助於神經細胞分化與存活
論文名稱(英文) Beta-amyloid peptide promotes neurons differentiation and survival
校院名稱 成功大學
系所名稱(中) 細胞生物及解剖學研究所
系所名稱(英) Institute of Cell Biology and Anatomy
學年度 93
學期 2
出版年 94
研究生(中文) 吳沛翊
研究生(英文) Pei-Yi Wu
電子信箱 pei19801108@yahoo.com.tw
學號 t9692402
學位類別 碩士
語文別 英文
論文頁數 53頁
口試委員 口試委員-陳淑姿
指導教授-郭余民
口試委員-曾淑芬
中文關鍵字 分化  存活  神經細胞  貝它糊蛋白 
英文關鍵字 beta-amyloid peptide  neuron  survival  differentiation 
學科別分類
中文摘要   阿滋海默氏症是高齡層的人類最容易罹患的一種癡呆症,這個疾病有兩個主要的病理特徵 : 第一個為神經細胞內的神經纖維糾結,主要由 tau 蛋白組成;第二個是大量堆積在細胞外的纖維化貝它糊蛋白。在腦中貝它糊蛋白不正常的聚集被廣泛的認為是造成阿滋海默氏症的最主要病因。然而,最近的研究卻指出貝它糊蛋白在促使神經細胞存活上扮演著重要的角色,而且也被認為具有促使神經先驅細胞分化的功能。對於這樣的觀點我提出以下的假設 : 我假設貝它糊蛋白的生理功能會隨著結構的改變而不同,也就是當貝它糊蛋白聚集成某一個特定形式的時候它可以促進神經的存活或分化,而當它進一步地聚集成另一種特定形式的時候反而會具有毒性。為了要取得不同聚集形式的貝它糊蛋白,我將貝它糊蛋白溶於2%的氨水中然後以1N HCl/5 mM Tris中和至中性(pH7.4)接著置於室溫下24小時。將這樣的貝它糊蛋白溶液經過分子篩膜的分離將聚集成不同大小的貝它糊蛋白分成五個部分: >1000、 300-1000、100-300、 30-100、 和 <30 kDa。我的實驗結果發現分子量介於30-100 kDa的貝它糊蛋白具有促使人類的神經瘤母細胞(SH-SY5Y)增生及分化的能力,而聚集成較大分子量的貝它糊蛋白卻反而導致細胞的死亡。同樣的情形也發生在以取自老鼠的初代神經細胞(primary neurons)為材料的實驗中。這些結果提供證據證實了當貝它糊蛋白聚集到30-100 kDa的程度時可以促使神經細胞的增生以及促進神經先驅細胞的分化。另外,在in vivo的實驗中發現30-100 kDa的貝它糊蛋白可以引起神經的再生,對於老鼠在短期記憶上也有進步的現象。至於貝它糊蛋白在生理上的真正功能仍需要進一步的被探討與驗証。
英文摘要   Alzheimer’s disease (AD) is the most common cause of dementia in aged humans. Two neuropathological lesions characterize the disease: intraneuronal neurofibrillary tangles, which are composed of the tau protein, and extracellular accumulation of fibrillar amyloid β peptide (Aβ). The abnormal aggregation of Aβ peptide in brain is generally considered as one of the major causes in the pathogenesis of AD. However, recent studies demonstrated that Aβ plays an important role in the viability of neuron. Furthermore, it was suggested that Aβ could promote neuron progenitor cells differentiation. In this regard, I hypothesize that the physiological function of Aβ is conformation-dependent. That is when A in certain aggregated forms, it may promote neuron survival and/or differentiation, while in certain more aggregated forms, it transforms into neurotoxic identity. To obtain different aggregated forms, Aβ was dissolved in 2% NH4OH, neutralized to pH7.4 by 1N HCl/5 mM Tris, and incubated at room temperature for 24 h. Various A aggregated sizes were then separated into >1000, 300-1000, 100-300, 30-100, and <30 kDa using membrane molecular sieving technique. My results indicated Aβ40 at 30-100 kDa possessing the ability to promote human neuroblastoma cell, SH-SY5Y, proliferation and differentiation, while the larger aggregates of Aβ induce the SH-SY5Y cell death. Such effects were also evident in the primary cortical neurons. These results suggest that Aβ peptide at the size of 30-100 kDa can promote neuron proliferation and induce neuronal progenitor cells differentiation. In vivo, the 30-100 kDa Aβ40 peptides could promote neurogenesis and enhance the short-term memory of mice. The physiological functions of Aβ require further clarification.
論文目次 ABSTRACT IN CHINESE…………………………………………………….. i
ABSTRACT……………………………………………………………………... ii
ACKNOWEDGE………………………………………………………………...iii
TABLE OF CONTENTS………………………………………………………. iv
LIST OF TABLES……………………………………………………………… v
LIST OF FIGURES…………………………………………………………….. vi

INTRODUCTION……………………………………………………………… 1
OBJECTIVE…………………………………………………………………... 11
MATERIAL AND METHODS……………………………………………… 12
RESULTS………………………………………………………………………. 24
DISCUSSION………………………………………………………………….. 29
REFERENCES………………………………………………………………... 34
FIGURES………………………………………………………………………. 43
ABOUT THE AUTHOR……………………………………………………….53
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