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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Alzheimer's disease peptide β-amyloid interacts with fibrinogen and induces its oligomerization
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Alzheimer's disease peptide β-amyloid interacts with fibrinogen and induces its oligomerization

机译：阿尔茨海默氏病肽β-淀粉样蛋白与纤维蛋白原相互作用并诱导其寡聚

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摘要

Increasing evidence supports a vascular contribution to Alzheimer's disease (AD), but a direct connection between AD and the circulatory system has not been established. Previous work has shown that blood clots formed in the presence of the β-amyloid peptide (Aβ), which has been implicated in AD, have an abnormal structure and are resistant to degradation in vitro and in vivo. In the present study, we show that Aβ specifically interacts with fibrinogen with a K_d of 26.3 ± 6.7 nM, that the binding site is located near the C terminus of the fibrinogen β-chain, and that the binding causes fibrinogen to oligomerize. These results suggest that the interaction between Aβ and fibrinogen modifies fibrinogen's structure, which may then lead to abnormal fibrin clot formation. Overall, our study indicates that the interaction between Aβ and fibrinogen may be an important contributor to the vascular abnormalities found in AD.
机译：越来越多的证据支持血管对阿尔茨海默氏病（AD）的贡献，但尚未建立AD与循环系统之间的直接联系。先前的研究表明，与AD有关的在β淀粉样肽（Aβ）存在下形成的血凝块具有异常的结构，并且对体外和体内的降解具有抵抗力。在本研究中，我们显示Aβ与血纤蛋白原特异性相互作用，K_d为26.3±6.7 nM，结合位点位于血纤蛋白原β链的C末端附近，并且该结合导致血纤蛋白原寡聚。这些结果表明，Aβ和纤维蛋白原之间的相互作用改变了纤维蛋白原的结构，然后可能导致异常的纤维蛋白凝块形成。总体而言，我们的研究表明Aβ和纤维蛋白原之间的相互作用可能是AD中发现的血管异常的重要因素。

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    Hyung Jin Ahn; Daria Zamolodchikov; Marta Cortes-Canteli; Erin H. Norris; J. Fraser Glickman; Sidney Strickland;

  • 作者单位

    Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY 10065;

    Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY 10065;

    Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY 10065;

    Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY 10065;

    High Throughput Screening Resource Center, The Rockefeller University, New York, NY 10065;

    Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY 10065;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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