碩士 / 國防醫學院 / 藥學研究所 / 105 / Alzheimer’s disease (AD) is a progressive neurodegenerative disease. It is the majority among dementia patients. The classical pathological hallmarks of AD are senile plaques and neurofibrillary tangles, which are located in the brain and neuronal cells. According to β-amyloid hypothesis, the toxic Aβ oligomers alter neuronal function and induce neuronal cells inflammation. Ultimately, the neuronal homeostasis is broken down and leads to clinical symptoms such as cognitive dysfunction and memory loss. Hyperphosphorylated taus tend to aggregate into neurofibrillary tangle and destabilize microtubules that are at the root of the tau pathology.
The development for the treatment of AD can be divided into two categories based on its pathological progression. One is aim to reduce Aβ quantity, such as β-secretase inhibitors, γ-secretase inhibitors, anti-Aβ monoclonal antibodies. The other is focusing on tau pathology, like heat shock protein 90 inhibitors, microtubules stabilizers, histone deacetylase 6 (HDAC 6) inhibitors. In this study, a series of new HDAC inhibitors were designed and synthesized by choosing 7-azaindole as the cap structure of the recognition space. Through screening on HDACs inhibition assay kit, the compound POBen is the most potent in the HDAC6 inhibition test among the tested compounds, while the compound MOBen is the weakest but most selective one. The results suggested that the skeleton of the linker portion can be optimized in further experiments to provide more potential candidates.
| Identifer | oai:union.ndltd.org:TW/105NDMC0551002 |
| Date | January 2017 |
| Creators | LIN, CHIA-YANG, 林家暘 |
| 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 | 167 |
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