The DOI matches its Crossref record; 57 of the 57 references it cites were found in a registry or an index.
Aberrant Expression of Mitotic Cdc2/Cyclin B1 Kinase in Degenerating Neurons of Alzheimer’s Disease Brain
Open accessAbstract
We have shown previously that M-phase phospho-epitopes accumulate in neuronal tau proteins incorporated into the hallmark neurofibrillary tangles (NFT) of Alzheimer’s disease (AD). In M phase, the epitopes are produced by cdc2/cyclin B1 kinase by a highly conserved mechanism believed to be quiescent in terminally differentiated neurons of adult brain. To determine whether an M-phase mechanism is possible in AD neurons, we first investigated the presence of cdc2 and cyclin B1 in AD. Both proteins were enriched in neurons with NFT and in neurons susceptible to NFT. An antibody specific for catalytically active cdc2 stained numerous NFT-containing neurons in AD but did not react with normal neurons. Double-labeling studies showed that active cdc2 and cyclin B1 coexist in AD neurons and co-localize with AD-specific mitotic phospho-epitopes. Mitotic kinase purified from AD and normal brain, using the yeast p13suc1 protein as affinity ligand, showed higher histone H1 phosphorylation activity in AD. Accordingly, the levels of cdc2 and cyclin B1 in p13suc1 fractions from AD were higher than normal. Consistent with a physiological relationship between NFT and mitotic kinase, NFT proteins co-purified with and became phosphorylated by the p13suc1-bound kinase in vitro. Furthermore, cdc2/cyclin B1 is the only one of several proline-directed kinases that created the TG/MC mitotic phospho-epitopes in recombinant tau in vitro. These findings suggest that aberrantly reexpressed cdc2/cyclin B1 in NFT-bearing neurons in AD brain contributes to the generation of M-phase phospho-epitopes in NFT.
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Cited by
Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
Guo, T., Zhang, D., Zeng, Y., Huang, T. Y., Xu, H., & Zhao, Y. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00391-7 · Cited by 994
The prolyl isomerase Pin1 restores the function of Alzheimer-associated phosphorylated tau protein
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Ectopic Cell Cycle Proteins Predict the Sites of Neuronal Cell Death in Alzheimer’s Disease Brain
Busser, J., Geldmacher, D. S., & Herrup, K. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-08-02801.1998 · Cited by 543
Cell cycle regulation in the postmitotic neuron: oxymoron or new biology?
Herrup, K., & Yang, Y. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2124 · Cited by 507
Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer’s disease
Yang, Y., Mufson, E. J., & Herrup, K. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-07-02557.2003 · Cited by 483
Metadata
- Authors
- Vincent, I., Jicha, G., Rosado, M., & Dickson, D. W.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1997-05-15
- Volume
- 17
- Issue
- 10
- Pages
- 3588-3598
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W1577877616
- Cited by
- 444
- References
- 57
- FWCI
- 12.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Vincent, I., Jicha, G., Rosado, M., & Dickson, D. W. (1997). Aberrant Expression of Mitotic Cdc2/Cyclin B1 Kinase in Degenerating Neurons of Alzheimer’s Disease Brain. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.17-10-03588.1997
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