碩士 / 國立陽明大學 / 生物藥學研究所 / 105 / Abstract
Owing to the advances in modern medicine, the average human life is gradually prolonged, accompanied by neurodegenerative diseases such as Alzheimer's disease (AD). However, there are currently no effective drugs for treating AD. So that the development of related drugs is urgent. In recent years, more and more studies have found that, in addition to the accumulation of plaques and neurofibrillary tangle which can be found in patient's brain, inflammation is also considered to be the third pathological features. Hence, anti-inflammatory drug is another potential treatment strategy for AD. Among this strategy, glial cells play the major role in neuroinflammation during the pathological progress of AD. The aim of this study is to investigate the anti-inflammatory effects of Sal F derivatives on the inflammatory response induced by lipopolysaccharide (LPS) and amyloid beta (Aβ), and its potential on AD treatment was evaluated. In order to look for the effective anti-inflammatory drugs, the effective drugs was first screened targeting on LPS-mediated activation, and then Aβ-mediated activation were further screened from the effective candidates screened targeting on LPS-mediated activation. The final screened drugs may therefore be used as the candidates for AD therapy. Our results showed that WTL 8-2, WTL 8-15, WTL 8-39, WTL 8-40, WTL 8-59, WTL 8-60, WTL 8-61, WTL 8-62 and WTL 8-70 were effective on the primary screening on LPS-mediated activation. Furthermore, WTL 8-59, WTL 8-60,WTL 8-61, WTL 8-62, WTL 8-70 were effective on the primary screening on Aβ + IFN-γ-mediated activation. To investigate whether the later five drugs are potential for AD treatment, the effects of these drugs on morphology change, phagocytosis ability and inflammation-related cytokine regulation of microglia were also investigated. It turns out that WTL 8-59 and WTL 8-60 show the best effect in the Aβ + IFN-γ-induced inflammatory model on recovering microglia into ramified morphology. WTL 8-59、WTL 8-60、WTL 8-62、WTL 8-70 reduce both TNF-α and IL-1β secretion. However, only WTL 8-59 did not reduce the ability of microglia to uptake Aβ. WTL 8-59 shows good effect on each aspect, Thus, WTL 8-59 is selected as the final candidate with potential for AD treatment form the Sal F derivatives and is worth for the future drug development.
| Identifer | oai:union.ndltd.org:TW/105YM005603005 |
| Date | January 2017 |
| Creators | Pei-Ru Zhu, 朱沛儒 |
| Contributors | Young-Ji Shiao, Chi-Ying Huang, 蕭永基, 黃奇英 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 47 |
Page generated in 0.0121 seconds