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HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer's disease.
Pao, Ping-Chieh; Patnaik, Debasis; Watson, L Ashley; Gao, Fan; Pan, Ling; Wang, Jun; Adaikkan, Chinnakkaruppan; Penney, Jay; Cam, Hugh P; Huang, Wen-Chin; Pantano, Lorena; Lee, Audrey; Nott, Alexi; Phan, Trongha X; Gjoneska, Elizabeta; Elmsaouri, Sara; Haggarty, Stephen J; Tsai, Li-Huei.
Afiliação
  • Pao PC; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Patnaik D; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Watson LA; Chemical Neurobiology Laboratory, Departments of Neurology and Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
  • Gao F; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Pan L; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Wang J; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Adaikkan C; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Penney J; Caltech Bioinformatics Resource Center at Beckman Institute of Caltech, Pasadena, CA, 91225, USA.
  • Cam HP; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Huang WC; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Pantano L; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Lee A; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Nott A; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Phan TX; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Gjoneska E; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Elmsaouri S; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Haggarty SJ; Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • Tsai LH; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Nat Commun ; 11(1): 2484, 2020 05 18.
Article em En | MEDLINE | ID: mdl-32424276
ABSTRACT
DNA damage contributes to brain aging and neurodegenerative diseases. However, the factors stimulating DNA repair to stave off functional decline remain obscure. We show that HDAC1 modulates OGG1-initated 8-oxoguanine (8-oxoG) repair in the brain. HDAC1-deficient mice display age-associated DNA damage accumulation and cognitive impairment. HDAC1 stimulates OGG1, a DNA glycosylase known to remove 8-oxoG lesions that are associated with transcriptional repression. HDAC1 deficiency causes impaired OGG1 activity, 8-oxoG accumulation at the promoters of genes critical for brain function, and transcriptional repression. Moreover, we observe elevated 8-oxoG along with reduced HDAC1 activity and downregulation of a similar gene set in the 5XFAD mouse model of Alzheimer's disease. Notably, pharmacological activation of HDAC1 alleviates the deleterious effects of 8-oxoG in aged wild-type and 5XFAD mice. Our work uncovers important roles for HDAC1 in 8-oxoG repair and highlights the therapeutic potential of HDAC1 activation to counter functional decline in brain aging and neurodegeneration.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dano ao DNA / Encéfalo / Envelhecimento / Estresse Oxidativo / DNA Glicosilases / Histona Desacetilase 1 / Doença de Alzheimer Limite: Animals Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dano ao DNA / Encéfalo / Envelhecimento / Estresse Oxidativo / DNA Glicosilases / Histona Desacetilase 1 / Doença de Alzheimer Limite: Animals Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos