| First Author | Sykora P | Year | 2015 |
| Journal | Nucleic Acids Res | Volume | 43 |
| Issue | 2 | Pages | 943-59 |
| PubMed ID | 25552414 | Mgi Jnum | J:223234 |
| Mgi Id | MGI:5648576 | Doi | 10.1093/nar/gku1356 |
| Citation | Sykora P, et al. (2015) DNA polymerase beta deficiency leads to neurodegeneration and exacerbates Alzheimer disease phenotypes. Nucleic Acids Res 43(2):943-59 |
| abstractText | 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 beta. 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/Polbeta(+/-) 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. |
