Chiang, H-C., Wang, L., Xie, Z. L., Yau, A., Zhong, Y. (April 2010) PI3 kinase signaling is involved in A beta-induced memory loss in Drosophila. Proceedings of the National Academy of Sciences of the United States of America, 107 (15). pp. 7060-7065. ISSN 0027-8424
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Abstract
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 beta-amyloid peptide (A beta)induced memory loss in the Drosophila brain. We began our inquiry into the molecular basis of this memory loss by studying A beta 42-induced enhancement of long-term depression. We found that long-term depression is restored to a normal level through inhibition of PI3K activity. A beta 42-induced PI3K hyperactivity is directly confirmed by immunostaining of the PI3K phosphorylation targets, phospholipids. Such observations lead to the following demonstration that A beta 42-induced memory loss can be rescued through genetic silencing or pharmacological inhibition of PI3K functions. Our data suggest that A beta 42 stimulates PI3K, which in turn causes memory loss in association with an increase in accumulation of A beta 42 aggregates.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | beta-amyloid Alzheimer's disease learning and memory PI3K ALZHEIMERS-DISEASE NEUROMUSCULAR-JUNCTION SYNAPTIC PLASTICITY IN-VIVO PROTEIN PEPTIDE PATHWAY AKT MELANOGASTER MODEL |
| Subjects: | diseases & disorders > mental disorders > delirium dementia cognitive disorders > Alzheimer's disease organism description > animal > insect > Drosophila bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes |
| CSHL Authors: | |
| Communities: | CSHL labs > Zhong lab |
| Depositing User: | CSHL Librarian |
| Date: | 13 April 2010 |
| Date Deposited: | 29 Sep 2011 14:35 |
| Last Modified: | 05 Jan 2018 17:51 |
| PMCID: | PMC2872421 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/15385 |
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