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首页> 外文期刊>Biochemistry >Mechanisms of Enzymatic Degradation of Amyloid Microfibrils GeneratingNanofilaments and Nanospheres Related to Cytotoxicityt
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Mechanisms of Enzymatic Degradation of Amyloid Microfibrils GeneratingNanofilaments and Nanospheres Related to Cytotoxicityt

机译:淀粉样蛋白微纤维的酶促降解的机制,与细胞毒性有关的壬丝和纳米球体

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摘要

Amyloid /3 (A/I) fibrils are found in the brain tissue of persons with Alzheimer's disease (AD),where they accumulate as plaques. One way to reduce the level of accumulation of AP in the brain andpotentially treat AD is with AP-degrading enzymes such as neprilysin (NEP) and insulin-degrading enzyme(IDE). However, enzymatic responses and degradation mechanisms of A/3 fibrils (crystalline-state A/3) havenot been investigated, particularly with respect to how to avoid cytotoxicity of the degradation products toneuronal cells. Thus, insight into mechanisms of enzymatic degradation of A/3 fibrils would be instructive as aroute to elucidating different structural features related to degradation and to cytotoxicity. We reportmechanisms of enzymatic degradation of AP with cross-/3 structures and show the series of steps involved inthe digestion of A/I microfibrils to nanospheres or nanofilaments by protease XIV or a-chymotrypsin,respectively. These degradation products, which contained almost the same secondary structures, exhibiteddifferent cytotoxicities, indicating that relationships between nanoassembled structures and cytotoxicity ofAP peptides are more significant than the sheet content. In addition, the enzymatic digestion at the Lys28loop region linking the two /I-sheets in AP fibrils is suggested as a key target related to cytotoxicity, a featurethat can be selectively targeted on the basis of the choice of protease.
机译:淀粉样蛋白/ 3(a / i)原纤维在阿尔茨海默病(Ad)的人的脑组织中发现,其中它们作为斑块积累。减少大脑中AP积累水平的一种方法和肛能治疗AD是具有AP降解的酶,例如Neprilysin(Nep)和胰岛素降解酶(IDE)。然而,研究了A / 3原纤维的酶反应和降解机制(结晶 - 状态A / 3)HAVENOT,特别是关于如何避免降解产物的细胞毒性正常细胞的细胞毒性。因此,欣赏到A / 3原纤维的酶促降解机制将是指导的,以阐明与降解和细胞毒性有关的不同结构特征。我们报告酶促降解AP的酶促,分别涉及通过蛋白酶XIV或A-Chymotrypsin消化对纳米球或纳丝纤维的含有微生物的一系列步骤。这些含有几乎相同的二级结构的降解产物表明纳米组织结构与细胞毒性之间的关系比片状含量更大。另外,将AP原纤维中的两个/ I片连接的Lys28Loop区的酶消化作为与细胞毒性有关的关键靶,可以基于蛋白酶的选择选择性地靶向细胞。

著录项

  • 来源
    《Biochemistry》 |2010年第15期|共7页
  • 作者

    Keiji Numata; David L. Kaplan;

  • 作者单位

    Department of Biomedical Engineering Tufts University 4 Colby Street Medford Massachusetts 02155;

    Department of Biomedical Engineering Tufts University 4 Colby Street Medford Massachusetts 02155;

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

    persons; structures; feature;

    机译:人员;结构;特征;

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