| The neuronal expression of MYC causes a neurodegenerative phenotype in a novel transgenic mouse. | |
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MedLine Citation:
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PMID: 19164506 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Many different proteins associated with the cell cycle, including cyclins, cyclin-dependent kinases, and proto-oncogenes such as c-MYC (MYC), are increased in degenerating neurons. Consequently, an ectopic activation of the cell cycle machinery in neurons has emerged as a potential pathogenic mechanism of neuronal dysfunction and death in many neurodegenerative diseases, including Alzheimer's disease. However, the exact role of cell cycle re-entry during disease pathogenesis is unclear, primarily because of the lack of relevant research models to study the effects of cell cycle re-entry on mature neurons in vivo. To address this issue, we developed a new transgenic mouse model in which forebrain neurons (CaMKII-MYC) can be induced to enter the cell cycle using the physiologically relevant proto-oncogene MYC to drive cell cycle re-entry. We show that such cell cycle re-entry results in neuronal cell death, gliosis, and cognitive deficits. These findings provide compelling evidence that dysregulation of cell cycle re-entry results in neurodegeneration in vivo. Our current findings, coupled with those of previous reports, strengthen the hypothesis that neurodegeneration in Alzheimer's disease, similar to cellular proliferation in cancer, is a disease that results from inappropriate cell cycle control. |
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Authors:
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Hyoung-gon Lee; Gemma Casadesus; Akihiko Nunomura; Xiongwei Zhu; Rudy J Castellani; Sandy L Richardson; George Perry; Dean W Felsher; Robert B Petersen; 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: 2009-01-22 |
Journal Detail:
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Title: The American journal of pathology Volume: 174 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2009 Mar |
Date Detail:
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Created Date: 2009-02-23 Completed Date: 2009-03-23 Revised Date: 2013-01-31 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 891-7 Citation Subset: AIM; IM |
Affiliation:
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Department of Pathology, Case Western Reserve University, 2103 Cornell Rd., Cleveland, OH 44106, USA. hyoung-gon.lee@case.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Cycle Gene Expression Regulation Genes, myc* Heredodegenerative Disorders, Nervous System / genetics*, pathology Hippocampus / physiology Humans Maze Learning Mice Mice, Transgenic Nerve Degeneration / genetics, pathology Neurons / physiology* Phenotype Reverse Transcriptase Polymerase Chain Reaction |
| Grant Support | |
ID/Acronym/Agency:
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AG028679/AG/NIA NIH HHS; AG030096/AG/NIA NIH HHS; AG031364/AG/NIA NIH HHS; R21 AG030096/AG/NIA NIH HHS; R21 AG030096-02/AG/NIA NIH HHS |
| Comments/Corrections | |
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