Sato K, Wakamiya A, Maeda T, Noguchi K, Takashima A, Imahori K
Mitsubishi Kasei Institute of Life Sciences, Tokyo.
J Biochem. 1995 Dec;118(6):1108-11. doi: 10.1093/oxfordjournals.jbchem.a124994.
Structure-neurotoxicity relationships of amyloid beta (25-35) peptide were studied by replacing each amino acid with Ala. In contrast to the general tendency in hydrophobicity-toxicity relationships, replacement of Asn27 yielded a more hydrophobic but less toxic analog and that of Met35 gave a less hydrophobic but more toxic one. Sedimentation profiles and CD spectra indicated that peptide aggregation via intermolecular beta-sheet formation is essential for the neurotoxicity of amyloid beta (25-35) peptide. The correlation between neurotoxicity and amyloid precursor protein accumulation suggested that the latter is one of the pathways of the neuronal death caused by amyloid beta protein.
通过将淀粉样β蛋白（25 - 35）肽中的每个氨基酸替换为丙氨酸，研究了其结构与神经毒性的关系。与疏水性 - 毒性关系的一般趋势相反，将Asn27替换后得到了一个疏水性更强但毒性更小的类似物，而将Met35替换后得到了一个疏水性更弱但毒性更强的类似物。沉降曲线和圆二色光谱表明，通过分子间β - 折叠形成的肽聚集对于淀粉样β蛋白（25 - 35）肽的神经毒性至关重要。神经毒性与淀粉样前体蛋白积累之间的相关性表明，后者是由淀粉样β蛋白引起的神经元死亡途径之一。
