DNA polymerase β deficiency leads to neurodegeneration and exacerbates Alzheimer disease phenotypes.
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| Abstract |
We explore the role of DNA damage processing in the progression of cognitive decline by creating a new mouse model. The new model is a cross of a common Alzheimer's disease (AD) mouse (3xTgAD), with a mouse that is heterozygous for the critical DNA base excision repair enzyme, DNA polymerase β. A reduction of this enzyme causes neurodegeneration and aggravates the AD features of the 3xTgAD mouse, inducing neuronal dysfunction, cell death and impairing memory and synaptic plasticity. Transcriptional profiling revealed remarkable similarities in gene expression alterations in brain tissue of human AD patients and 3xTg/Polβ(+/-) mice including abnormalities suggestive of impaired cellular bioenergetics. Our findings demonstrate that a modest decrement in base excision repair capacity can render the brain more vulnerable to AD-related molecular and cellular alterations.
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| Authors | Peter Sykora, Magdalena Misiak, Yue Wang, Somnath Ghosh, Giovana S Leandro, Dong Liu, Jane Tian, Beverly A Baptiste, Wei-Na Cong, Boris M Brenerman, Evandro Fang, Kevin G Becker, Royce J Hamilton, Soumya Chigurupati, Yongqing Zhang, Josephine M Egan, Deborah L Croteau, David M Wilson 3rd, Mark P Mattson, Vilhelm A Bohr |
| Journal | Nucleic acids research (Nucleic Acids Res) Vol. 43 Issue 2 Pg. 943-59 (Jan 2015) ISSN: 1362-4962 [Electronic] England |
| PMID | 25552414 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't) |
| Copyright | Published by Oxford University Press on behalf of Nucleic Acids Research 2014. This work is written by US Government employees and is in the public domain in the US. |
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