PI3 kinase signaling is involved in Aβ-induced memory loss in Drosophila

Hsueh Cheng Chiang, Lei Wang, Zuolei Xie, Alice Yau, Yi Zhong

研究成果: Article同行評審

101 引文 斯高帕斯(Scopus)

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.

原文English
頁(從 - 到)7060-7065
頁數6
期刊Proceedings of the National Academy of Sciences of the United States of America
107
發行號15
DOIs
出版狀態Published - 2010 4月 13

All Science Journal Classification (ASJC) codes

  • 多學科

指紋

深入研究「PI3 kinase signaling is involved in Aβ-induced memory loss in Drosophila」主題。共同形成了獨特的指紋。

引用此