HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer's disease.
Nat Commun
; 11(1): 2484, 2020 05 18.
Article
em En
| MEDLINE
| ID: mdl-32424276
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
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Encéfalo
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Envelhecimento
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Estresse Oxidativo
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DNA Glicosilases
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Histona Desacetilase 1
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Doença de Alzheimer
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article