Amyloid beta interacts with the amyloid precursor protein: a potential toxic mechanism in Alzheimer's disease.
Amyloid beta interacts with the amyloid precursor protein: a potential toxic mechanism in Alzheimer's disease.
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发表时间：
2000
影响因子：
25
通讯作者：
A. Lorenzo;M. Yuan;Z. Zhang;P. Paganetti;C. Sturchler-Pierrat,;M. Staufenbiel;J. Mautino;F. S. Vigo;B. Sommer;B. Yankner
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文献类型：
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作者：
A. Lorenzo;M. Yuan;Z. Zhang;P. Paganetti;C. Sturchler-Pierrat,;M. Staufenbiel;J. Mautino;F. S. Vigo;B. Sommer;B. Yankner
淀粉样β蛋白(Abeta)在大脑中的沉积是阿尔茨海默病(AD)的一个标志。Abeta的纤维状形态具有神经毒性，尽管其毒性机制尚不清楚。我们发现，将Abeta转化为纤维状显著增加了与特定神经细胞膜蛋白的结合，包括淀粉样前体蛋白(APP)。皮质神经元中纤维蛋白Aβ结合的细胞表面全息APP的纳摩尔浓度。培养的APP缺陷型神经元对Abeta神经毒性的易感性降低，提示Abeta神经毒性与APP有关。因此，Abeta的毒性可能是通过纤维Abeta与神经细胞膜蛋白，特别是APP的相互作用而介导的。因此，Abeta-APP的相互作用可能会导致AD的神经元退化，这让人想起Pron的致病机制。
Amyloid beta protein (Abeta) deposition in the brain is a hallmark of Alzheimer's disease (AD). The fibrillar form of Abeta is neurotoxic, although the mechanism of its toxicity is unknown. We showed that conversion of Abeta to the fibrillar form markedly increased binding to specific neuronal membrane proteins, including amyloid precursor protein (APP). Nanomolar concentrations of fibrillar Abeta bound cell-surface holo-APP in cortical neurons. Reduced vulnerability of cultured APP-null neurons to Abeta neurotoxicity suggested that Abeta neurotoxicity involves APP. Thus Abeta toxicity may be mediated by the interaction of fibrillar Abeta with neuronal membrane proteins, notably APP. An Abeta-APP interaction reminiscent of the pathogenic mechanism of prions may thus contribute to neuronal degeneration in AD.