| Neuronal cell cycle re-entry mediates Alzheimer disease-type changes. | |
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MedLine Citation:
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PMID: 17095196 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Evidence showing the ectopic re-expression of cell cycle-related proteins in specific vulnerable neuronal populations in Alzheimer disease led us to formulate the hypothesis that neurodegeneration, like cancer, is a disease of inappropriate cell cycle control. To test this notion, we used adenoviral-mediated expression of c-myc and ras oncogenes to drive postmitotic primary cortical neurons into the cell cycle. Cell cycle re-entry in neurons was associated with increased DNA content, as determined using BrdU and DAPI, and the re-expression of cyclin B1, a marker for the G2/M phase of the cell cycle. Importantly, we also found that cell cycle re-entry in primary neurons leads to tau phosphorylation and conformational changes similar to that seen in Alzheimer disease. This study establishes that the cell cycle can be instigated in normally quiescent neuronal cells and results in a phenotype that shares features of degenerative neurons in Alzheimer disease. As such, our neuronal cell model may be extremely valuable for the development of novel therapeutic strategies. |
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Authors:
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Andrew McShea; Hyoung-gon Lee; Robert B Petersen; Gemma Casadesus; Inez Vincent; Nancy J Linford; Jens-Oliver Funk; Robert A Shapiro; Mark A Smith |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-10-03 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1772 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2007 Apr |
Date Detail:
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Created Date: 2007-03-19 Completed Date: 2007-04-26 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 467-72 Citation Subset: IM |
Affiliation:
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Department of Biology, CombiMatrix Corp, Mukilteo, WA 98275, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alzheimer Disease
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pathology* Animals Cell Cycle / physiology* Disease Models, Animal Embryo, Mammalian Humans Immunohistochemistry Kinetics Neurons / pathology* Rats Rats, Sprague-Dawley tau Proteins / metabolism |
| Chemical | |
Reg. No./Substance:
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0/tau Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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