DNA polymerase beta deficiency leads to neurodegeneration and exacerbates Alzheimer disease phenotypes

Autor(es):Mostrar menos -

Sykora, Peter ^[1] ; Misiak, Magdalena ^{[2, 1]} ; Wang, Yue ^[2] ; Ghosh, Somnath ^[1] ; Leandro, Giovana S. ^{[3, 1]} ; Liu, Dong ^[2] ; Tian, Jane ^[1] ; Baptiste, Beverly A. ^[1] ; Cong, Wei-Na ^[4] ; Brenerman, Boris M. ^[1] ; Fang, Evandro ^[1] ; Becker, Kevin G. ^[5] ; Hamilton, Royce J. ^[1] ; Chigurupati, Soumya ^[2] ; Zhang, Yongqing ^[6] ; Egan, Josephine M. ^[4] ; Croteau, Deborah L. ^[1] ; Wilson, III, David M. ^[6] ; Mattson, Mark P. ^[2] ; Bohr, Vilhelm A. ^[6]

Afiliação do(s) autor(es)

^[1] NIA IRP, Lab Mol Gerontol, Biomed Res Ctr, Baltimore, MD 21224 - USA

^[2] NIA IRP, Lab Neurosci, Biomed Res Ctr, Baltimore, MD 21224 - USA

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] NIA IRP, Lab Clin Invest, Biomed Res Ctr, Baltimore, MD 21224 - USA

^[5] NIA IRP, Genet Lab, Biomed Res Ctr, Baltimore, MD 21224 - USA

^[6] Wilson, David M., III, NIA IRP, Lab Mol Gerontol, Biomed Res Ctr, Baltimore, MD 21224 - USA

• Tipo de documento: Artigo Científico
• Fonte: Nucleic Acids Research; v. 43, n. 2, p. 943-959, JAN 30 2015.
• Citações Web of Science: 38

Resumo

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/Pol beta(+/-) 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. (AU)

• Processo FAPESP: 13/11052-1 - Influência da deficiência de reparo do DNA no desenvolvimento e progressão da Doença de Alzheimer em modelo de camundongo
• Beneficiário: Giovana da Silva Leandro
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado