CDT2‐controlled cell cycle reentry regulates the pathogenesis of Alzheimer's disease
Open accessAbstract
Introduction: Altered cell cycle reentry has been observed in Alzheimer's disease (AD). Denticleless (DTL) was predicted as the top driver of a cell cycle subnetwork associated with AD. Methods: We systematically investigated DTL expression in AD and studied the molecular, cellular, and behavioral endophenotypes triggered by DTL overexpression. Results: We experimentally validated that CDT2, the protein encoded by DTL , activated cyclin‐dependent kinases through downregulating P21, which induced tau hyperphosphorylation and Aβ toxicity, two hallmarks of AD. We demonstrated that cyclin‐dependent kinases inhibition by roscovitine not only rescued CDT2‐induced cognitive defects but also reversed expression changes induced by DTL overexpression. RNA‐seq data from the DTL overexpression experiments revealed the molecular mechanisms underlying CDT2 controlled cell cycle reentry in AD. Discussion: These findings provide new insights into the molecular mechanisms of AD pathogenesis and thus pave a way for developing novel therapeutics for AD by targeting AD specific cell cycle networks and drivers.
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The reason for tau hyperphosphorylation is a mutation in the tau genes or dysregulation of kinases and phosphatases.
“The reason stated for the hyper phosphorylation is a mutation in the tau genes or dysregulation of kinases as mentioned below and phosphatases which catalyze the phosphorylation process [7].”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [7]
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Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease
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“The reason stated for the hyper phosphorylation is a mutation in the tau genes or dysregulation of kinases as mentioned below and phosphatases which catalyze the phosphorylation process [7].”
BackgroundChallenges and hopes for Alzheimer’s disease
Tatulian, S. A. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.01.016 · Cited by 291 · see citing works
- Authors
- Huang, F., Wang, M., Liu, R., Wang, J., Schadt, E., Haroutunian, V., Katsel, P., Zhang, B., & Wang, X.
- Affiliations
- Huazhong University of Science and Technology (CN)
- Icahn School of Medicine at Mount Sinai (US)
- James J. Peters VA Medical Center (US)
- Nantong University (CN)
- Corresponding author
- Zhang, Bin
- Wang, Xiaochuan
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2018-10-12
- Volume
- 15
- Issue
- 2
- Pages
- 217-231
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC6758558
- OpenAlex
- W2896843995
- Cited by
- 47
- References
- 56
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 9 · 2023: 8 · 2022: 7 · 2021: 8 · 2020: 6 · 2019: 1
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- Funders
- National Natural Science Foundation of China (31528010, 81571255, 31771114)
- Topics
- Health Sciences › Medicine › Physiology › 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
- Alzheimer's disease, Cdt2
- MeSH terms
- Alzheimer Disease, Animals, Cell Cycle, Humans, Nuclear Proteins, Phosphorylation, Down-Regulation, tau Proteins, Mice
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