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首页> 外文期刊>Journal of Molecular Biology >Cholesterol, a modulator of membrane-associated Abeta-fibrillogenesis and neurotoxicity.
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Cholesterol, a modulator of membrane-associated Abeta-fibrillogenesis and neurotoxicity.

机译：胆固醇，一种与膜相关的Abeta纤维形成和神经毒性的调节剂。

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Recent studies have suggested that cholesterol, an important determinant of the physical state of biological membranes, plays a significant role in the development of Alzheimer's disease. We have employed in situ scanning probe microscopy, fluorescence anisotropy, and electron microscopy to investigate how cholesterol levels within total brain lipid bilayers effect amyloid beta-peptide (Abeta)-assembly. Fluorescence anisotropy measurements revealed that the relative fluidity of the total brain lipid membranes was influenced by the level of cholesterol and the addition of Abeta40 resulted in a decrease in the overall vesicle fluidity. In situ scanning probe microscopy performed on supported planar bilayers of total brain lipid revealed a correlation between membrane fluidity, as influenced by cholesterol level, and the extent of Abeta-insertion and subsequent fibrillogenesis. These observations were consistent with fluorescence microscopy studies of PC-12 and SH-SY5Y cell lines exposed to exogenous Abeta, which revealed an inverse correlation between membrane cholesterol level, and Abeta-cell surface binding and subsequent cell death. These results collectively suggest that Abeta-cell surface interactions are mediated by cellular cholesterol levels, the distribution of cholesterol throughout the cell, and membrane fluidity. Copyright 2001 Academic Press.
机译：最近的研究表明，胆固醇是生物膜物理状态的重要决定因素，在阿尔茨海默氏病的发展中起着重要作用。我们采用了原位扫描探针显微镜，荧光各向异性和电子显微镜来研究总脑脂质双层中的胆固醇水平如何影响淀粉样β肽（Abeta）组装。荧光各向异性测量显示，总脑脂质膜的相对流动性受胆固醇水平的影响，Abeta40的添加导致总囊泡流动性下降。对总脑脂质的支持平面双层进行的原位扫描探针显微镜检查显示，受胆固醇水平影响的膜流动性与Abeta插入程度和随后的原纤维形成之间存在相关性。这些观察结果与暴露于外源Abeta的PC-12和SH-SY5Y细胞系的荧光显微镜研究一致，该研究揭示了膜胆固醇水平与Abeta细胞表面结合和随后的细胞死亡之间呈负相关。这些结果共同表明，Abeta细胞表面相互作用是由细胞胆固醇水平，胆固醇在整个细胞中的分布以及膜的流动性介导的。版权所有2001学术出版社。

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