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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >PI3 kinase signaling is involved in Ap-induced memory loss in Drosophila
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PI3 kinase signaling is involved in Ap-induced memory loss in Drosophila

机译：PI3激酶信号传导与果蝇中Ap诱导的记忆丧失有关

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摘要

Multiple intracellular signals are altered in Alzheimer's disease brain tissues, including the PI3K/Akt pathway. However, the pathological relevance of such alterations is poorly understood. In vitro studies yield results that seem to be consistent with the conventional perception in which an up-regulation of the cell survival pathway, PI3K pathway, is protective in Alzheimer's disease pathogenesis. The current in vivo genetic approach, however, reveals that inhibition of the PI3K pathway leads to rescuing of the β-amyloid peptide (Aβ)-induced memory loss in the Drosophila brain. We began our inquiry into the molecular basis of this memory loss by studying Aβ42-induced enhancement of long-term depression. We found that long-term depression is restored to a normal level through inhibition of PI3K activity. Aβ42-induced PI3K hyperactivity is directly confirmed by immunostaining of the PI3K phosphorylation targets, phospholipids. Such observations lead to the following demonstration that Aβ42-induced memory loss can be rescued through genetic silencing or pharmacological inhibition of PI3K functions. Our data suggest that Aβ42 stimulates PI3K, which in turn causes memory loss in association with an increase in accumulation of Aβ42 aggregates.
机译：阿尔茨海默氏病脑组织（包括PI3K / Akt途径）中的多个细胞内信号发生了改变。但是，这种改变的病理相关性了解甚少。体外研究得出的结果似乎与传统观念一致，在传统观念中，细胞存活途径（PI3K途径）的上调在阿尔茨海默氏病的发病机理中具有保护作用。然而，当前的体内遗传学方法表明，PI3K途径的抑制导致果蝇脑中挽救β-淀粉样肽（Aβ）诱导的记忆力丧失。通过研究Aβ42诱导的长期抑郁症的增强，我们开始研究这种记忆丧失的分子基础。我们发现长期的抑郁症可以通过抑制PI3K活性而恢复到正常水平。通过对PI3K磷酸化靶标磷脂进行免疫染色，直接证实了Aβ42诱导的PI3K过度活跃。这些观察结果导致以下证明：可以通过基因沉默或药理抑制PI3K功能来挽救Aβ42诱导的记忆丧失。我们的数据表明，Aβ42刺激PI3K，继而引起记忆丧失，伴随Aβ42聚集体积累的增加。

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  • 作者

    Hsueh-Cheng Chiang; Lei Wang; Zuolei Xie; Alice Yau; Yi Zhong;

  • 作者单位

    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724 Department of Neuroscience, State University of New York, Stony Brook, NY 11794;

    Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China;

    JoeKai, Inc., Beijing 100084, China;

    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724;

    Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724 Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China;

  • 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);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    β-amyloid; Alzheimer's disease; learning and memory; PI3K;

    机译：β-淀粉样蛋白阿尔茨海默氏病;学习和记忆;PI3K;

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