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c-Abl tyrosine kinase modulates tau pathology and Cdk5 phosphorylation in AD transgenic mice
Open accessAbstract
The c-Abl tyrosine kinase is an important link in signal transduction pathways that promote cytoskeletal rearrangement and apoptotic signalling. We have previously shown that amyloid-β-peptide (Aβ) activates c-Abl. Herein we show that c-Abl participates in Aβ-induced tau phosphorylation through Cdk5 activation. We found that intraperitoneal administration of STI571, a specific inhibitor for c-Abl kinase, decreased tau phosphorylation in the APPswe/PSEN1ΔE9 transgenic mouse brain. In addition, when neurons were treated with Aβ we observed: (i) an increase in active c-Abl and tau phosphorylation, (ii) the prevention of tau phosphorylation by STI571 and (iii) the inhibition of c-Abl expression by shRNA, as well as the expression of a c-Abl kinase death mutant, decreased AT8 and PHF1 signals. Furthermore, the increase of c-Abl was associated with Tyr15 phosphorylation of Cdk5 and its association with c-Abl. Brains from APPswe/PSEN1ΔE9 mice showed higher levels of c-Abl and phospho-Cdk5 than wild-type mice. Moreover, STI571 treatment decreased the phospho-Cdk5 levels. Together, the evidence suggests that activation of c-Abl by Aβ promotes tau phosphorylation through Tyr15 phosphorylation-mediated Cdk5 activation.
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Metadata
- Authors
- Cancino, G. I., Perez de Arce, K., Castro, P. U., Toledo, E. M., von Bernhardi, R., & Alvarez, A. R.
- Affiliations
- Pontificia Universidad Católica de Chile (CL)
- Corresponding author
- Alvarez, Alejandra R.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 32
- Issue
- 7
- Pages
- 1249-1261
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2012589975
- Cited by
- 110
- References
- 67
- Citations by year
- 2026: 1 · 2025: 11 · 2024: 5 · 2023: 10 · 2022: 9 · 2021: 7 · 2020: 8 · 2019: 5 · 2018: 6 · 2017: 2 · 2016: 7 · 2015: 7 · 2014: 8 · 2013: 8 · 2012: 4
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- green
- americanae.aecid.es
- Licence
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Americanae (AECID Library) (submittedVersion, other-oa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- Funders
- FONDECYT (1040782, 1080221)
- FONDAP (13980001)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- c-Abl kinase, tau phosphorylation, cyclin-dependent kinase 5, amyloid-beta, Alzheimer's disease, imatinib, tau pathology, kinase inhibitors
- MeSH terms
- Alzheimer Disease, Animals, Cells, Cultured, Disease Models, Animal, Hippocampus, Humans, Mice, Transgenic, Phosphorylation, Proto-Oncogene Proteins c-abl, Amyloid beta-Protein Precursor, tau Proteins, Rats, Sprague-Dawley, Mice, Rats
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