Cited by 96Alzheimer's disease research and treatmentsRedox biology and oxidative stressAmyotrophic Lateral Sclerosis Research

Oxidative damage to the promoter region of SQSTM1/p62 is common to neurodegenerative disease

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Du, Yifeng, Wooten, Michael C., Wooten, Marie W.·2009·Neurobiology of Disease

Abstract

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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Crossref · 10.1016/j.nbd.2009.05.015

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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].”

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Authors
Du, Y., Wooten, M. C., & Wooten, M. W.
Affiliations
Auburn University (US)
Corresponding author
  • Wooten, Michael C.
  • Wooten, Marie W.
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2009-08
Volume
35
Issue
2
Pages
302-310
ISSN
0969-9961 (ISSN-L)
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
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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