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Cited by 185

The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.

The Insulin/Akt Signaling Pathway Is Targeted by Intracellular β-Amyloid

Lee, Han-Kyu, Kumar, Pravir, Fu, Qinghao, Rosen, Kenneth M., Querfurth, Henry W.·2009·Molecular Biology of the Cell
DOI 10.1091/mbc.e08-07-0777
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Abstract

Intraneuronal β-amyloid (Aβ i) accumulates early in Alzheimer's disease (AD) and inclusion body myositis. Several organelles, receptor molecules, homeostatic processes, and signal transduction components have been identified as sensitive to Aβ. Although prior studies implicate the insulin-PI3K-Akt signaling cascade, a specific step within this or any essential metabolic or survival pathway has not emerged as a molecular target. We tested the effect of Aβ42 on each component of this cascade. In AD brain, the association between PDK and Akt, phospho-Akt levels and its activity were all decreased relative to control. In cell culture, Aβ i expression inhibited both insulin-induced Akt phosphorylation and activity. In vitro experiments identified that β-amyloid (Aβ), especially oligomer preparations, specifically interrupted the PDK-dependent activation of Akt. Aβ i also blocked the association between PDK and Akt in cell-based and in vitro experiments. Importantly, Aβ did not interrupt Akt or PI3K activities (once stimulated) nor did it affect more proximal signal events. These results offer a novel therapeutic strategy to neutralize Aβ-induced energy failure and neuronal death.

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Crossref · 10.1091/mbc.e08-07-0777

Cites

14 of 14 references verified0 citation errors · 0 not checkable

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  • Aβ causes insulin resistance by interruption of phosphoinositide-dependent kinase-1 (PDK) activity through binding with its target protein kinase B (PKB/Akt).

    “Lee et al showed that Aβ causes insulin resistance by interruption of phosphoinositide‐dependent kinase‐1 (PDK) activity through binding with its target protein kinase B (PKB/Akt).”

    From BACE1: More than just a β‐secretase (2022) · cites this paper as [98]

Citations

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Metadata

Authors
Lee, H.-K., Kumar, P., Fu, Q., Rosen, K. M., & Querfurth, H. W.
Affiliations
Department of Neurology, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA 02135
Venue
Molecular Biology of the Cell
Publisher
American Society for Cell Biology (ASCB)
Published
2009-03
Volume
20
Issue
5
Pages
1533-1544
ISSN
  • 1059-1524
  • 1939-4586
DOI
10.1091/mbc.e08-07-0777
Cited by
185
References
14
Language
en

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