碩士 / 國立陽明大學 / 生物化學研究所 / 90 / Alzheimer’s disease is a neurodegenerative disease that leads to progressive dementia and neuronal death. Currently, the pathogenesis of this disease is still not yet clear. The main histopathological hallmarks of Alzheimer’s disease are the senile plaques within the cerebral cortex and the neurofibrillary tangles within the nerve cells. The primary component of senile plaques is a 39-42 amino acid hydrophobic peptide, b-amyloid peptide, which is derived from proteolysis of a much larger membrane-spanning protein known as b-amyloid precursor protein. The b-amyloid peptide is a soluble peptide, which can be detected in blood and cerebrospinal fluid. However, under certain environmental condition, it will polymerize at a very slow rate. The aggregation process converts monomer, soluble b-amyloid peptide to insoluble fibrils that eventually precipitate as amyloid plaques. Recent studies have suggested that b-amyloid peptide has neurotoxic properties in the aggregated state. Suppression or prevention of the aggregation of b-amyloid peptide maybe an appropriate therapeutic strategy. Our approach is based on that small molecules that can bind to b-amyloid peptides may interfere with its aggregation. By applying two-dimensional heteronuclear NMR spectroscopy, we can easily find these molecules. Furthermore, by solving high-resolution three-dimensional structures of these complexes we may obtain detailed information of the interactions between the small molecules and b-amyloid peptides. These information can be applied to structure-based rational drug design and developing small molecule therapeutic agents for the treatment of Alzheimer’s disease.
Identifer | oai:union.ndltd.org:TW/090YM000107043 |
Date | January 2002 |
Creators | Feng I Chu, 朱峰儀 |
Contributors | Ta Hsien Lin, 林達顯 |
Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
Language | zh-TW |
Detected Language | English |
Type | 學位論文 ; thesis |
Format | 81 |
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