The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Presenilin 1 associates with glycogen synthase kinase-3β and its substrate tau
Open accessAbstract
Families bearing mutations in the presenilin 1 (PS1) gene develop Alzheimer’s disease. Previous studies have shown that the Alzheimer-associated mutations in PS1 increase production of amyloid β protein (Aβ 1–42 ). We now show that PS1 also regulates phosphorylation of the microtubule-associated protein tau. PS1 directly binds tau and a tau kinase, glycogen synthase kinase 3β (GSK-3β). Deletion studies show that both tau and GSK-3β bind to the same region of PS1, residues 250–298, whereas the binding domain on tau is the microtubule-binding repeat region. The ability of PS1 to bring tau and GSK-3β into close proximity suggests that PS1 may regulate the interaction of tau with GSK-3β. Mutations in PS1 that cause Alzheimer’s disease increase the ability of PS1 to bind GSK-3β and, correspondingly, increase its tau-directed kinase activity. We propose that the increased association of GSK-3β with mutant PS1 leads to increased phosphorylation of tau.
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Cites
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Cited by
Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders
Ballatore, C., Lee, V. M.-Y., & Trojanowski, J. Q. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2194 · Cited by 2,174
WNT and β-catenin signalling: diseases and therapies
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GSK-3α regulates production of Alzheimer's disease amyloid-β peptides
Phiel, C. J., Wilson, C. A., Lee, V. M.-Y., & Klein, P. S. (2003) · Nature · doi:10.1038/nature01640 · Cited by 1,196
The GSK3 hypothesis of Alzheimer’s disease
Hooper, C., Killick, R., & Lovestone, S. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.05194.x · Cited by 1,191
Roles of tau protein in health and disease
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Metadata
- Authors
- Takashima, A., Murayama, M., Murayama, O., Kohno, T., Honda, T., Yasutake, K., Nihonmatsu, N., Mercken, M., Yamaguchi, H., Sugihara, S., & Wolozin, B.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1998-08-04
- Volume
- 95
- Issue
- 16
- Pages
- 9637-9641
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2053791137
- Cited by
- 409
- References
- 9
- FWCI
- 17.26
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Presenilin 1 associates with glycogen synthase kinase-3β and its substrate tau. https://app.cochat.ai/papers/10.1073/pnas.95.16.9637
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- Takashima, A., Murayama, M., Murayama, O., Kohno, T., Honda, T., Yasutake, K., Nihonmatsu, N., Mercken, M., Yamaguchi, H., Sugihara, S., & Wolozin, B. (1998). Presenilin 1 associates with glycogen synthase kinase-3β and its substrate tau. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.95.16.9637
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