Oxidative damage to the promoter region of SQSTM1/p62 is common to neurodegenerative disease
Open accessAbstract
Recently we reported that declined SQSTM1/p62 expression in Alzheimer disease brain was age-correlated with oxidative damage to the p62 promoter. The objective of this study was to examine whether oxidative damage to the p62 promoter is common to DNA recovered from brain of individuals with neurodegenerative disease. Increased 8-OHdG staining was observed in brain sections from Alzheimer's disease (AD), Parkinson disease (PD), Huntington disease (HD), Frontotemporal dementia (FTD), and Pick's disease compared to control subjects. In parallel, the p62 promoter exhibited elevated oxidative damage in samples from various diseases compared to normal brain, and damage was negatively correlated with p62 expression in FTD samples. Oxidative damage to the p62 promoter induced by H2O2 treatment decreased its transcriptional activity. In keeping with this observation, the transcriptional activity of a Sp-1 element deletion mutant displayed reduced stimulus-induced activity. These findings reveal that oxidative damage to the p62 promoter decreased its transcriptional activity and might therefore account for decreased expression of p62. Altogether these results suggest that pharmacological means to increase p62 expression may be beneficial in delaying the onset of neurodegeneration.
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Mutations detected in the SQSTM1 promoter region are associated with reduced SQSTM1 protein levels in familial ALS-FTD.
“Additionally, mutations detected in the SQSTM1 promoter region are associated with reduced SQSTM1 protein levels in familial ALS-FTD [132,133].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [132]
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Self-citation
- Authors
- Du, Y., Wooten, M. C., & Wooten, M. W.
- Affiliations
- Auburn University (US)
- Corresponding author
- Wooten, Michael C.
- Wooten, Marie W.
- ORCID
- Du, Yifeng
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 35
- Issue
- 2
- Pages
- 302-310
- ISSN
- 0969-9961 (ISSN-L)
- PMC
- PMC2718328
- OpenAlex
- W1981648285
- Cited by
- 96
- References
- 75
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 9 · 2020: 5 · 2019: 10 · 2018: 7 · 2017: 4 · 2016: 8 · 2015: 6 · 2014: 7 · 2013: 5 · 2012: 10
- FWCI
- 4.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- U.S. Public Health Service (33661)
- National Institute of Neurological Disorders and Stroke (R01NS033661)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- p62, oxidative DNA damage, neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, Huntington's disease, frontotemporal dementia, Pick's disease, 8-hydroxy-2'-deoxyguanosine, promoter transcriptional activity, hydrogen peroxide
- MeSH terms
- Sequestosome-1 Protein, Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cell Line, Dementia, Female, Humans, Huntington Disease, Hydrogen Peroxide, Male, Middle Aged, Parkinson Disease, Promoter Regions, Genetic, Transcription, Genetic, Oxidants, Oxidative Stress, Neurodegenerative Diseases, Pick Disease of the Brain, Adaptor Proteins, Signal Transducing
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