AGGREGATION STATE AND NEUROTOXIC PROPERTIES OF ALZHEIMER BETA-AMYLOID PEPTIDE
AGGREGATION STATE AND NEUROTOXIC PROPERTIES OF ALZHEIMER BETA-AMYLOID PEPTIDE
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DOI：
10.1006/neur.1995.0003
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发表时间：
1995-03-01
期刊：
影响因子：
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通讯作者：
ROBERTS, GW
中科院分区：
文献类型：
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作者：
HOWLETT, DR;JENNINGS, KH;ROBERTS, GW
研究了β-淀粉样蛋白（β A）1-40肽在溶液中的合成批次的行为。β A1-40对PC 12细胞毒性测定的影响取决于在应用于细胞之前肽的水溶液的预孵育时间。通过刚果红与淀粉样纤维的结合定量评估的β A1-40的固定化也在研究的168 h孵育期内以时间依赖性方式增加。在不存在任何预孵育的情况下，刚果红结合的程度在两个合成的不同批次的肽之间不同。随后孵育期间原纤维形成的发展速率在两个批次之间也不同，并且似乎与对细胞活力的影响平行。红光光谱分析揭示了两个批次的β-折叠形成以及肽之间的其他更细微的构象差异。β A1-40批次的电子显微镜检查证实了原纤维发生和发展的差异。在高倍放大下，两批原纤维均呈现螺旋结构。结果表明，β A1-40的神经毒性的发展与肽的纤维状态有关。
The behaviour of synthetic batches of beta-amyloid (beta A) 1-40 peptide in solution has been studied. The effects of beta A1-40 on a PC12 cell toxicity assay was dependent upon the time of preincubation of an aqueous solution of the peptide before application to the cells. Fibrillization of the beta A1-40, quantitatively assessed by the binding of Congo red to amyloid fibrils, also increased in a time dependent manner over the 168 h incubation period studied. The degree of Congo red binding, in the absence of any preincubation, differed between two synthetically distinct batches of the peptide. The rate of development of fibril formation during subsequent incubation also differed between the two batches and appeared to parallel the effects on cell viability. Infra-red spectroscopic analysis revealed beta-sheet formation for both batches and other more subtle conformational differences between the peptides. Electron microscope examination of the batches of beta A1-40 confirmed the difference in occurrence and development of fibrils. At high magnification, fibrils of both batches exhibited a helical structure. The results suggest that the development of neurotoxicity of beta A1-40 is related to the fibrillar state of the peptide.