碩士 / 國防醫學院 / 藥學研究所 / 106 / Alzheimer’s disease (AD) is the most common form of dementia characterized by the deposition of β-amyloid 42 plaques and neurofibrillary tau tangles. This leads to neuronal loss in specific areas of the brain. Abnormal tau phosphorylation and subsequent accumulation of neurofibrillary tau tangles was proposed to compromise microtubule dynamics and neuronal function. Hyperphosphorylated taus also lead to dysfunctional mitochondria, reduced axonal transport, abnormal aggregation of misfolded proteins, and increased oxidative stress in AD brain.
The development for the treatment of AD can be divided into two categories based on its pathological progression. One is aiming to reduce Aβ quantity, and the other is focusing on tau pathology. alpha-Tubulin, major components of tau protein, is a non-histone substrate of HDAC6, thus considering that HDAC6 can be an attractive target for drug development for the neurodegenerative disease. The recent failure of Aβ- targeted therapeutics in Phase III clinical trials suggests that it is timely and prudent to consider alternative drug discovery strategies for Alzheimer's disease. In this study, a series of new HDAC inhibitors were designed and synthesized by choosing indazole with an aromatic group as the cap structure of the recognition space. These synthetic compounds will be screened on HDACs inhibitory assays in due course.
| Identifer | oai:union.ndltd.org:TW/106NDMC0551002 |
| Date | January 2018 |
| Creators | TANG, HSI-YAO, 唐熙堯 |
| 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 | 146 |
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