碩士 / 國立臺灣師範大學 / 生命科學系 / 104 / Alzheimer’s disease (AD) is a neurodegenerative disorder that cause cognitive impairment. The pathological features of AD are neurofibrillary tangles (NFTs) cause by tau protein hyper-phosphorylation,insoluble β-amyloid (Aβ) plaques by Aβ accumulation, and neuron loss.There are no curative therapies currently available for AD patients until now. The control of histone acetylation and deacetylation has been recognized as one of major epigenetic regulatory mechanisms for specific gene expression. Histone deacetylases (HDACs) make the histones more tightly by removing the acetyl groups from histones, which in turn suppresses the gene transcription and causes many diseases. It has been reported that HDAC inhibitors (HDACi) could alleviate transcription suppression and show neuroprotective effect in several neurodegenerative diseases. In thisstudy, the mouse primary hippocampal neurons treated with oligomeric Aβ25-35was used to screen potential HDAC inhibitors forAD. The identified potential HDACi compound was applied to AD miceand the molecular mechanisms of the HDACi was further elucidated.We found that NC106 HDAC inhibitor could increase neuronal numbers, neuritic length, and branch numbersagainst the oligomeric Aβ25-35-induced neurotoxicityin primary hippocampal neuronal culture. In addition, we found that the neuroprotective effects of NC106 was better in high dose than in low dose in the primary hippocampal neuronal culture treated with oligomeric Aβ25-35. The administration of high doseNC106 also attenuated the anxiety and short-term memory of the AD mice. Reducing the levels of Aβ deposition, tau protein phosphorylation, neuroinflammation, and increasing the levels of presynaptic protein synaptophysin, serotonergic neurons were identified in the B6 mice with acute bilateral intrahippocampal CA1 injection of oligomeric Aβ25-35. Therefore,NC106 could be a potential therapeutic compoundfor AD.
| Identifer | oai:union.ndltd.org:TW/104NTNU5112123 |
| Date | January 2016 |
| Creators | Huang, Hsin-Yu, 黃莘淯 |
| Contributors | Hsieh, Hsiu-Mei, 謝秀梅 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 99 |
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