Document Detail


Neuronal cell cycle re-entry mediates Alzheimer disease-type changes.
MedLine Citation:
PMID:  17095196     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-10-03
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1772     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-03-19     Completed Date:  2007-04-26     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  467-72     Citation Subset:  IM    
Affiliation:
Department of Biology, CombiMatrix Corp, Mukilteo, WA 98275, USA.
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MeSH Terms
Descriptor/Qualifier:
Alzheimer Disease / 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:
0/tau Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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