| Summary: | 碩士 === 慈濟大學 === 分子生物及細胞生物研究所 === 92 === Biochemical analysis reveals that the main constituent of Alzeheimer disease is a small peptide containing 39-43 amino acid residues and referred to as the amyloid-b (Ab). Fibrillar Ab, but not soluble Ab, is neurotoxic and can cause neuronal death both in vitro and in vivo. The formation of Ab fibrillness is highly correlated with the sequence and conformation of Ab. Although it is generally valid that the change of conformation to b-sheet is the key state to form the fibrillary tangle, it still remains unclear whether the sequence and conformation is correlated and result in neurotoxicity. In order to fully explore the relationship between sequence and neurotoxicity, we examined wild- type and truncated Abs and its correlation between the structure and neurotoxicity. In combination of spectroscopic and cellular techniques, result showed that the hydrophobic C-terminus, particularly the sequence in 17-21, 25-35 and 41-42, is highly correlated to the neurotoxicity. Deletion of sequences 17-21, 25-35 or 41-42 can significantly reduce the toxicity. On the other hand, the N-terminus and sequence 22-24 and 36-40 seem to have little effect on Ab toxicity. We hypothesis that the sequences 17-21 and 25-35 form an intramolecular b-sheet via sequence 22-24 which are the main causes of neurotoxicity. However, this hypothesis needs further investigation.
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