Cdk5 and the non-catalytic arrest of the neuronal cell cycle
Open accessAbstract
Cyclin-dependent kinase 5 (Cdk5) is a nontraditional Cdk that is primarily active in postmitotic neurons. An important core function of Cdk5 involves regulating the migration and maturation of embryonic post-mitotic neurons. These developmental roles are dependent on its kinase activity. Initially, there was little evidence indicating a role for Cdk5 in normal cell cycle regulation. Recent data from our lab, however, suggest that Cdk5 plays a crucial role as a cell cycle suppressor in normal post-mitotic neurons and neuronal cell lines. It performs this foundation in a kinase independent manner. Cdk5 normally found in both nucleus and cytoplasm, but it exits the nucleus in neurons risk to death in an AD patient's brain. The shift in sub-cellular location is accompanied by cell cycle re-entry and neuronal death. This "new" function of Cdk5 raises cautions in the design of Cdk5-directed drugs for the therapy of neurodegenerative diseases.
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Cdk5 has been suggested as a cell-cycle suppressor in post-mitotic neurons.
“Another protein (Cdk5), which is not associated with the cell-cycle, has been suggested as a cell-cycle suppressor in post-mitotic neurons”
From Repair of Oxidative DNA Damage, Cell-Cycle Regulation and Neuronal Death May Influence the Clinical Manifestation of Alzheimer’s Disease (2014) · cites this paper as [42]
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- [28]Gilmore EC Ohshima T Goffinet AM Kulkarni AB Herrup K Cyclin-dependent kinase 5-deficient mice demonstrate novel developmental arrest in cerebral cortex J Neurosci 1998 18 6370 7 9698328 PMC6793186
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- Authors
- Zhang, J., & Herrup, K.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Herrup, Karl
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2008-11-15
- Volume
- 7
- Issue
- 22
- Pages
- 3487-3490
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- PMC
- PMC3743047
- OpenAlex
- W1988585385
- Cited by
- 44
- References
- 70
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 2 · 2022: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 6 · 2014: 3 · 2013: 2 · 2012: 6
- FWCI
- 0.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Cycle (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- National Institute on Aging (R01AG024494)
- National Institute of Neurological Disorders and Stroke (R01NS020591)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Keywords
- cyclin-dependent kinase 5, postmitotic neurons, cell cycle re-entry, neuronal cell death, Alzheimer's disease
- MeSH terms
- Animals, Cell Cycle, Humans, Neurons, Neurodegenerative Diseases, Cyclin-Dependent Kinase 5
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