HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer’s disease
Open accessAbstract
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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HDAC1-deficient mice show DNA damage accumulation and cognitive impairment during aging.
“HDAC1-deficient mice show DNA damage accumulation and cognitive impairment during aging [126].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [126]
HDAC1 modulates OGG1-initiated 8-oxoguanine repair in the brain.
“the report of Pao et al. 2021 shows that histone deacetylase (HDAC)1 modulates OGG1-initated 8-oxoguanine (8-oxoG) repair in the brain [126].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [126]
In the 5XFAD mouse model of AD, elevated 8-oxoG is accompanied by reduced HDAC1 activity and downregulation of a gene set critical for brain function.
“this work showed elevated 8-oxoG along with reduced HDAC1 activity and downregulation of a gene set critical for brain function in the 5XFAD mouse model of AD”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [126]
HDAC1 has important roles in 8-oxoG repair and HDAC1 activation has therapeutic potential to counteract functional decline in brain aging and neurodegeneration.
“uncovering important roles for HDAC1 in 8-oxoG repair and highlights the therapeutic potential of HDAC1 activation to counteract the functional decline in brain aging and neurodegeneration [126].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [126]
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- Authors
- Pao, P.-C., Patnaik, D., Watson, L. A., Gao, F., Pan, L., Wang, J., Adaikkan, C., Penney, J., Cam, H. P., Huang, W.-C., Pantano, L., Lee, A., Nott, A., Phan, T. X., Gjoneska, E., Elmsaouri, S., Haggarty, S. J., & Tsai, L.-H.
- Affiliations
- Massachusetts Institute of Technology (US)
- Harvard University (US)
- California Institute of Technology (US)
- University of California San Diego (US)
- National Institutes of Health (US)
- Corresponding author
- Tsai, Li-Huei
- ORCID
- Venue
- Nature Communications
- Published
- 2020-05-18
- Volume
- 11
- Issue
- 1
- Pages
- 2484-2484
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7235043
- OpenAlex
- W3025772309
- Cited by
- 216
- References
- 72
- Citations by year
- 2026: 25 · 2025: 45 · 2024: 38 · 2023: 37 · 2022: 41 · 2021: 23 · 2020: 7
- FWCI
- 8.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- IslandScholar (University of Prince Edward Island) (submittedVersion, cc-by)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (AG046174)
- U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NS102730)
- Glenn Foundation for Medical Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Keywords
- HDAC1, OGG1, 8-oxoguanine, oxidative DNA damage repair, brain aging, Alzheimer's disease, DNA glycosylase, transcriptional repression, cognitive impairment, 5xFAD mice, neurodegeneration, DNA damage accumulation
- MeSH terms
- Acetylation, Aging, Alzheimer Disease, Animals, Astrocytes, Base Sequence, Benzophenones, Brain, Cognition, Cognition Disorders, DNA Damage, Guanine, Memory, Mice, Inbred C57BL, Neurons, Promoter Regions, Genetic, Down-Regulation, Mice, Knockout, Oxidative Stress, DNA Glycosylases, Histone Deacetylase 1, Gene Ontology
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