Therapeutic strategies targeting amyloid-β aggregation for Alzheimer's disease / 以amyloid-β 聚集為目標的阿茲海默氏症治療策略

碩士 / 國立臺灣師範大學 / 生命科學研究所 / 101 / Alzheimer's disease is the most common form of dementia that is pathologically characterized by the presence of extracellular amyloid plaques formed from Aβ peptide and intracellular neurofibrillary tangles formed from tau protein. Aggregation is often based on the formation of cross-β-structure and may be inhibited by disrupting the hydrogen bonds between sheets. Thus screening for indole, polyphenol derivatives and herbal medicines might find out potential inhibitors of Aβ peptide aggregation. To do this, thioflavin T assay was used to screen the synthetic compounds. Also, Aβ42 was fused to the N-terminus of GFP to couple the aggregation state with the fluorescence of GFP and used to generate Tet-On SH-SY5Y cell and 293 cell clones. Tet-On 293 cells were used to screen herbal extracts and natural or synthetic compounds. Inhibitors that retard or block Aβ42 aggregation can be distinguished by the increasing green fluorescent signal. The effective concentration of the tested herbs and compounds will be determined by using a high content analysis system that combines automated microscopy and automated image analysis in 293 AD model. In this study, 10 herbal extracts and synthetic compounds which could significantly increase green fluorescent signal were identified. Among the 10 compounds examined, NTNU-043, NTNU-057, NTNU-059, NTNU-071, NC009-1 and NC009-2 effectively increased green fluorescent signal and enhanced Hsp27 expression.

Identiferoai:union.ndltd.org:TW/101NTNU5112007
Date January 2013
CreatorsChen-Hsiang Huang, 黃鉦翔
ContributorsGuey-Jen Lee-Chen, 李桂楨
Source SetsNational Digital Library of Theses and Dissertations in Taiwan
Languagezh-TW
Detected LanguageEnglish
Type學位論文 ; thesis
Format55

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