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首页> 外文期刊>Biochemistry >Mechanism of Amyloid β-Protein Aggregation Mediated by GM1 Ganglioside Clusters
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Mechanism of Amyloid β-Protein Aggregation Mediated by GM1 Ganglioside Clusters

机译：GM1神经节苷脂簇介导的淀粉样蛋白β-蛋白聚合的机制

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摘要

It is widely accepted that the conversion of the soluble, nontoxic amyloid β-protein (Aβ) monomer to aggregated toxic Aβ rich in β-sheet structures is central to the development of Alzheimer’s disease. However, the mechanism of the abnormal aggregation of Aβ in vivo is not well understood. We have proposed that ganglioside clusters in lipid rafts mediate the formation of amyloid fibrils by Aβ, the toxicity and physicochemical properties of which are different from those of amyloids formed in solution. In this paper, the mechanism by which Aβ-(1-40) fibrillizes in raftlike lipid bilayers composed of monosialoganglioside GM1, cholesterol, and sphingomyelin was investigated in detail on the basis of singular-value decomposition of circular dichroism data and analysis of fibrillization kinetics. At lower protein densities in the membrane (Aβ:GM1 ratio of less than ～0.013), only the helical species exists. At intermediate protein densities (Aβ:GM1 ratio between ～0.013 and ～0.044), the helical species and aggregated β-sheets (～15-mer) coexist.However, the β-structure is stable and does not form larger aggregates. At Aβ:GM1 ratios above ～0.044, the β-structure is converted to a second, seed-prone β-structure. The seed recruits monomers from the aqueous phase to form amyloid fibrils. These results will shed light on a molecular mechanism for the pathogenesis of the disease.
机译：众所周度地普遍认为，可溶性的无毒淀粉样蛋白β-蛋白（Aβ）单体与富含β-片状结构的毒性Aβ的含有毒性的毒性Aβ是含有阿尔茨海默病的疾病的核心。然而，体内Aβ的异常聚集的机制尚不清楚。我们提出了脂肪筏中的神经节苷脂簇通过Aβ介导淀粉样蛋白原纤维，其毒性和物理化学性质与在溶液中形成的淀粉样蛋白的形成不同。本文在圆形二色性数据的奇异值分解和原纤化动力学分析的基础上，详细研究了由MonoSialoganglioside Gm1，胆固醇和鞘氨酰式组成的Aβ-（1-40）纤维植物纤维化的机制。 。在膜中的较低蛋白质密度（Aβ：GM1比例小于〜0.013），只有螺旋物种存在。在中间蛋白质密度（Aβ：GM1比〜0.013和〜0.044之间），螺旋物种和聚集β-薄片（〜15-MER）共存。但是，β结构是稳定的，不形成较大的聚集体。在Aβ：GM1比以上〜0.044的比例，β-结构转化为第二种种子 - 易于β结构。种子从水相开始单体以形成淀粉样蛋白原纤维。这些结果将在疾病发病机制上阐明光线。

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  • 来源
    《Biochemistry》 |2011年第29期|共8页
  • 作者

    Keisuke Ikeda; Takahiro Yamaguchi; Saori Fukunaga; Masaru Hoshino; Katsumi Matsuzaki;

  • 作者单位

    Graduate School of Pharmaceutical Sciences Kyoto University 46-29 Yoshida-Shimoadachi-cho Sakyo-ku Kyoto 606-8501 Japan;

    Graduate School of Pharmaceutical Sciences Kyoto University 46-29 Yoshida-Shimoadachi-cho Sakyo-ku Kyoto 606-8501 Japan;

    Graduate School of Pharmaceutical Sciences Kyoto University 46-29 Yoshida-Shimoadachi-cho Sakyo-ku Kyoto 606-8501 Japan;

    Graduate School of Pharmaceutical Sciences Kyoto University 46-29 Yoshida-Shimoadachi-cho Sakyo-ku Kyoto 606-8501 Japan;

    Graduate School of Pharmaceutical Sciences Kyoto University 46-29 Yoshida-Shimoadachi-cho Sakyo-ku Kyoto 606-8501 Japan;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
  • 关键词

    Mechanism; Aggregation; Clusters;

    机译：机制;聚合;群集;

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