The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Increasing Cu bioavailability inhibits Aβ oligomers and tau phosphorylation
Open accessAbstract
Cognitive decline in Alzheimer's disease (AD) involves pathological accumulation of synaptotoxic amyloid-β (Aβ) oligomers and hyperphosphorylated tau. Because recent evidence indicates that glycogen synthase kinase 3β (GSK3β) activity regulates these neurotoxic pathways, we developed an AD therapeutic strategy to target GSK3β. The strategy involves the use of copper- bis (thiosemicarbazonoto) complexes to increase intracellular copper bioavailability and inhibit GSK3β through activation of an Akt signaling pathway. Our lead compound Cu II (gtsm) significantly inhibited GSK3β in the brains of APP/PS1 transgenic AD model mice. Cu II (gtsm) also decreased the abundance of Aβ trimers and phosphorylated tau, and restored performance of AD mice in the Y-maze test to levels expected for cognitively normal animals. Improvement in the Y-maze correlated directly with decreased Aβ trimer levels. This study demonstrates that increasing intracellular copper bioavailability can restore cognitive function by inhibiting the accumulation of neurotoxic Aβ trimers and phosphorylated tau.
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Cites
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
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Cited by
Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis
Prasad, A., Bharathi, V., Sivalingam, V., Girdhar, A., & Patel, B. K. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00025 · Cited by 774
Biochemistry of Amyloid -Protein and Amyloid Deposits in Alzheimer Disease
Masters, C. L., & Selkoe, D. J. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006262 · Cited by 542
Self-citationMetabolism and functions of copper in brain
Scheiber, I. F., Mercer, J. F. B., & Dringen, R. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2014.01.002 · Cited by 506
Copper in the brain and Alzheimer’s disease
Hung, Y. H., Bush, A. I., & Cherny, R. A. (2010) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-009-0600-y · Cited by 498
Self-citationBiological metals and metal-targeting compounds in major neurodegenerative diseases
Barnham, K. J., & Bush, A. I. (2014) · Chem. Soc. Rev. · doi:10.1039/c4cs00138a · Cited by 497
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Metadata
- Authors
- Crouch, P. J., Hung, L. W., Adlard, P. A., Cortes, M., Lal, V., Filiz, G., Perez, K. A., Nurjono, M., Caragounis, A., Du, T., Laughton, K., Volitakis, I., Bush, A. I., Li, Q.-X., Masters, C. L., Cappai, R., Cherny, R. A., Donnelly, P. S., White, A. R., & Barnham, K. J.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2009-01-13
- Volume
- 106
- Issue
- 2
- Pages
- 381-386
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2014210332
- Cited by
- 278
- References
- 43
- FWCI
- 16.53
- Type
- journal article
- Language
- en
- Open access
- green
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- Crouch, P. J., Hung, L. W., Adlard, P. A., Cortes, M., Lal, V., Filiz, G., Perez, K. A., Nurjono, M., Caragounis, A., Du, T., Laughton, K., Volitakis, I., Bush, A. I., Li, Q.-X., Masters, C. L., Cappai, R., Cherny, R. A., Donnelly, P. S., White, A. R., & Barnham, K. J. (2009). Increasing Cu bioavailability inhibits Aβ oligomers and tau phosphorylation. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0809057106
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
