碩士 / 國防醫學院 / 藥學研究所 / 105 / Alzheimer’s disease (AD), the most common form of progressive dementia, is characterized by the presence of extracellular senile plagues and intra-neuronal fibrillary tangles. -Amyloid (A) peptides, the proteolytic products derived from sequential cleavage of a transmembrane protein-APP by -secretase and -secretase, are major components of the senile plaques.
Autophagic dysfunctions are referred as a pathologic mechanism for neurodegenerative diseases, such as AD. Some study indicated that beclin-1, a protein with a key role in autophagy, was decreased in the brain of AD patients. Moreover, inhibition of ErbB2 not only upregulated expression of beclin-1 but also attenuated Aproduction, suggesting that ErbB2 is a novel target for AD.
In this study, a series of new quinazoline derivatives as ErbB2 inhibitors was designed and synthesized based on the modification of the butynamide group of the lead CL-387,785 for improving selectivity and potency. Modulation of A autophagy by measuring the -secretase activity and the change of amount of A hrough ErbB2 inhibition in cell-based assays will be carried out to explore the potential therapies for AD.
| Identifer | oai:union.ndltd.org:TW/105NDMC0551003 |
| Date | January 2017 |
| Creators | Lin, Shi-Pang, 林仕邦 |
| Contributors | Hu, Ming-Kuan, 胡明寬 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 150 |
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