Cited by 263Alzheimer's disease research and treatmentsProtein Kinase Regulation and GTPase SignalingNeuroinflammation and Neurodegeneration Mechanisms

Exposure of rat hippocampal neurons to amyloid β peptide (25–35) induces the inactivation of phosphatidyl inositol-3 kinase and the activation of tau protein kinase I/glycogen synthase kinase-3β

Takashima, Akihiko, Noguchi, Kaori, Michel, Gilles, Mercken, Marc, Hoshi, Minako, Ishiguro, Koichi, Imahori, Kazutomo·1996·Neuroscience Letters

Abstract

Exposure of rat hippocampal neurons to the peptide amyloid beta (A beta) (25-35) as well as A beta (1-40) peptides enhances phosphorylation of tau to a paired helical filament (PHF)-state through activation of tau protein kinase I (TPK I)/glycogen synthase kinase-3 beta (GSK-3 beta) [Busciglio, J., Lorenzo, A., Yeh, J. and Yankner, B.A., Neuron, 14 (1995) 879-888; Takashima, A., Ishiguro, K., Noguchi, K., Michel, G., Hoshi, M., Sato, K., Takahashi, M., Hoshino, T., Uchida, T. and Imahori, K., Neurosci. Meeting Abstr., 671 (1995) 17]. In order to examine the effects of A beta treatment on intracellular signaling mechanism, we have investigated the role of phosphatidyl inositol-3 (PI-3) kinase in the phosphorylation of tau. A beta (25-35) exposure induced an inactivation of PI-3 kinase and an activation of TPK I/GSK-3 beta in rat hippocampal culture. Wortmannin, an inhibitor of PI-3 kinase, also activated TPK I/GSK-3 beta, leading to an enhancement of tau phosphorylation and neuronal death in hippocampal culture. These results suggest that A beta (25-35) inhibition of PI-3 kinase results in the activation of TPK I/GSK-3 beta, the phosphorylation of tau, and resultant neuronal death in rat hippocampal neurons.

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Crossref · 10.1016/0304-3940(95)12257-5

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  • GSK3β can orchestrate pathological tau phosphorylation at over two-dozen disease-associated sites.

    “The GSK3β can orchestrate pathological tau-phosphorylation at over two-dozen disease-associated sites [181–184].”

    From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [183]

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Authors
Takashima, A., Noguchi, K., Michel, G., Mercken, M., Hoshi, M., Ishiguro, K., & Imahori, K.
Corresponding author
Takashima, Akihiko
Venue
Neuroscience Letters
Publisher
Elsevier BV
Published
1996-01
Volume
203
Issue
1
Pages
33-36
ISSN
0304-3940 (ISSN-L)
OpenAlex
W1986537744
Cited by
260
References
18
Citations by year
2026: 5 · 2025: 9 · 2024: 5 · 2023: 9 · 2022: 4 · 2021: 9 · 2020: 5 · 2019: 11 · 2018: 12 · 2017: 3 · 2016: 3 · 2015: 7 · 2014: 15 · 2013: 13 · 2012: 13
FWCI
3.21
Type
journal article
Language
en
Open access
closed
Locations
  • Neuroscience Letters (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
amyloid beta 25-35, Aβ40, phosphatidylinositol 3-kinase, glycogen synthase kinase-3β, tau phosphorylation, paired helical filaments, hippocampal neurons, neuronal cell death, wortmannin, Alzheimer's disease
MeSH terms
Wortmannin, Alzheimer Disease, Androstadienes, Animals, Cells, Cultured, Dose-Response Relationship, Drug, Enzyme Inhibitors, Glycogen Synthase, Hippocampus, Phosphotransferases, Amyloid beta-Protein Precursor, tau Proteins, Rats

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