Key Features
Enhance your research with our curated data sets and powerful platform features. Pluto Bio makes it simple to find and use the data you need.
Learn MoreUnrepaired DNA damage contributes to brain aging and neurodegenerative diseases. However, the factors stimulating DNA repair activity to stave off age-associated functional decline remain obscure. Here, we show that histone deacetylase 1 (HDAC1) modulates DNA repair in the aging brain via targeting OGG1 of the base excision repair pathway. Mice deficient in HDAC1 display age-associated accumulation of DNA damage in the brain and cognitive impairment. HDAC1 interacts with and positively stimulates OGG1, a DNA glycosylase that primarily acts on 8-oxoguanine (8-oxoG), a type of oxidative DNA damage associated with transcriptional repression. Loss of HDAC1 leads to impaired OGG1 activity, 8-oxoG accumulation at the promoters of a subset of genes critical for brain function, and transcriptional repression. Moreover, we observe elevated 8-oxoG lesions along with reduced HDAC1 activity and downregulation of a similar set genes in the 5XFAD mouse model of Alzheimers disease (AD). Notably, pharmacological activation of HDAC1 confers protection against the deleterious effects of 8-oxoG lesions in the brains of aged wild-type and 5XFAD mice. Our work uncovers an important role for HDAC1 in the repair of 8-oxoG lesions and highlights HDAC1 activation as a novel therapeutic strategy to counter functional decline during brain aging and neurodegeneration. SOURCE: Li-Huei Tsai (lhtsai_geo@hotmail.com) - Li-Huei Tsai MIT
View on GEOView in PlutoEnhance your research with our curated data sets and powerful platform features. Pluto Bio makes it simple to find and use the data you need.
Learn MoreUse Pluto's intuitive interface to analyze and visualize data for this experiment. Pluto's platform is equipped with an API & SDKs, making it easy to integrate into your internal bioinformatics processes.
Read about post-pipeline analysisView quality control data and experiment metadata for this experiment.
Request imports from GEO or TCGA directly within Pluto Bio.
Chat with our Scientific Insights team