| Cdk5 acts as a mediator of neuronal cell cycle re-entry triggered by amyloid-beta and prion peptides. | |
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MedLine Citation:
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PMID: 19158499 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cyclin-dependent kinase 5 (Cdk5) is a serine-threonine kinase important for different cellular processes. Involved in tau protein hyperphosphorylation and apoptotic neuronal death, two main neuropathological markers of Alzheimer's disease (AD) and Prion-related encephalopathies (PRE), Cdk5 also participates in cell cycle regulation. However, the precise relationship between cell cycle reactivation and Cdk5 dysregulation in AD and PRE remains unclear. To determine Cdk5 involvement in the triggering of an abortive cell cycle by amyloid-beta (Abeta) and prion (PrP) peptides, associated with AD and PRE pathogenesis, we examined the levels/activation of several cell cycle-associated proteins in cultured cortical neurons treated with Abeta1-40 and PrP106-126 peptides. Peptide treatments significantly increased Cdk4, phospho-retinoblastoma and proliferating cell nuclear antigen (PCNA) levels, whereas phospho-histone H3 remained invariable, suggesting cell cycle arrest before the M phase. Moreover, Abeta1-40 and PrP106-126 largely augmented the number of PCNA-immunoreactive cells with fragmented nuclei. The Cdk5 inhibitor roscovitine and the calpain inhibitor MDL28170 prevented the alterations in cell cycle markers induced by both peptides. The data obtained suggest that Abetaand PrP peptides induced neuronal cell cycle re-entry through a mechanism involving Cdk5 dysregulation. Therefore, cell cycle reactivation mediated by Cdk5 can underlie the neurodegenerative processes that occur in AD and PRE. |
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Authors:
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João P Lopes; Catarina R Oliveira; Paula Agostinho |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Cell cycle (Georgetown, Tex.) Volume: 8 ISSN: 1551-4005 ISO Abbreviation: Cell Cycle Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2009-01-23 Completed Date: 2009-02-25 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 101137841 Medline TA: Cell Cycle Country: United States |
Other Details:
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Languages: eng Pagination: 97-104 Citation Subset: IM |
Affiliation:
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Center for Neuroscience and Cell Biology, Faculty of Medicine, Biochemistry Institute, University of Coimbra, Coimbra, Portugal. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amyloid beta-Protein
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pharmacology* Animals Apoptosis / drug effects Cell Cycle / drug effects* Cerebral Cortex / cytology Cyclin D1 / metabolism Cyclin-Dependent Kinase 4 / metabolism Cyclin-Dependent Kinase 5 / metabolism* G2 Phase / drug effects Mitosis / drug effects Models, Biological Nerve Degeneration / enzymology, pathology Neurons / cytology*, drug effects, enzymology* Peptides / pharmacology* Phosphorylation / drug effects Prions / pharmacology* Proliferating Cell Nuclear Antigen / metabolism Rats Rats, Wistar Retinoblastoma Protein / metabolism Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Amyloid beta-Protein; 0/Peptides; 0/Prions; 0/Proliferating Cell Nuclear Antigen; 0/Retinoblastoma Protein; 136601-57-5/Cyclin D1; EC 2.7.1.37/Cdk5 protein, rat; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinase 5 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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