ArticleScientific reports2021
MTH1 and OGG1 maintain a low level of 8-oxoguanine in Alzheimer's brain, and prevent the progression of Alzheimer's pathogenesis.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 51 citations in OpenAlex.
- ZBP1 in Neuroinflammation and Neurodegeneration: Z-Nucleic-Acid Sensing, RHIM Signalling and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- TH5487 specifically targets NLRP3 in FCAS patients resistant to MCC950.Communications biology · 2026Article
- Nucleobase catalysts for the enzymatic activation of 8-oxoguanine DNA glycosylase 1.RSC chemical biology · 2026Article
- 8-Oxoguanine: A Lesion, an Epigenetic Mark, or a Molecular Signal?International journal of molecular sciences · 2025Review
- Giving an Enzyme Scissors: Serotonin Derivatives as Potent Organocatalytic Switches for DNA Repair Enzyme OGG1.Journal of medicinal chemistry · 2025Article
- High-Frequency, Low-Intensity Pulsed Electric Field and N-Acetylcysteine Synergistically Protect SH-SY5Y Cells Against Hydrogen Peroxide-Induced Cell Damage In Vitro.Antioxidants (Basel, Switzerland) · 2025Article
- Sequential release of MTH1 inhibitor and chemotherapeutic drug using a pH-sensitive polymeric delivery system induces apoptosis in human tongue squamous cell carcinoma CAL-27 cells in vitro.World journal of surgical oncology · 2025Article
- Increased nucleotide metabolism alleviates Alzheimer's disease pathology.Cell death & disease · 2025Article
- Esculetin inhibits ferroptosis after ICH by promoting NUDT1-mediated m7G methylation modification of GPX4.Scientific reports · 2025Article
- Molecular Duality of OGG1: From Genomic Guardian to Redox-Sensitive Modulator in Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Organocatalytic Switches of DNA Glycosylase OGG1 Catalyze a Highly Efficient AP-Lyase Function.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Alzheimer's disease as an auto-innate immune pathology with potential cell trans-differentiation and enhanced trained immunity in 3xTg-AD mouse model.Journal of Alzheimer's disease : JAD · 2025Article
- NEIL3 influences adult neurogenesis and behavioral pattern separation via WNT signaling.Cellular and molecular life sciences : CMLS · 2025Article
- World no-tobacco: effects of second-hand smoke (SHS) and vapors on the developing and adult brain.Frontiers in pharmacology · 2025Review
- Role of MTH1 in oxidative stress and therapeutic targeting of cancer.Redox biology · 2024Review
- Noradrenaline Protects Human Microglial Cells (HMC3) Against Apoptosis and DNA Damage Induced by LPS and AβInternational journal of molecular sciences · 2024Article
- Human 8-oxoguanine glycosylase OGG1 binds nucleosome at the dsDNA ends and the super-helical locations.Communications biology · 2024Article
- Adaptive and Maladaptive DNA Breaks in Neuronal Physiology and Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Effect of kynurenic acid on enzymatic activity of the DNA base excision repair pathway in specific areas of the sheep brain.Scientific reports · 2024Article
- Novel Techniques for Mapping DNA Damage and Repair in the Brain.International journal of molecular sciences · 2024Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
8-Oxoguanine (8-oxoG), a major oxidative base lesion, is highly accumulated in Alzheimer's disease (AD) brains during the pathogenic process. MTH1 hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, thereby avoiding 8-oxo-dG incorporation into DNA. 8-OxoG DNA glycosylase-1 (OGG1) excises 8-oxoG paired with cytosine in DNA, thereby minimizing 8-oxoG accumulation in DNA. Levels of MTH1 and OGG1 are significantly reduced in the brains of sporadic AD cases. To understand how 8-oxoG accumulation in the genome is involved in AD pathogenesis, we established an AD mouse model with knockout of Mth1 and Ogg1 genes in a 3xTg-AD background. MTH1 and OGG1 deficiency increased 8-oxoG accumulation in nuclear and, to a lesser extent, mitochondrial genomes, causing microglial activation and neuronal loss with impaired cognitive function at 4-5 months of age. Furthermore, minocycline, which inhibits microglial activation and reduces neuroinflammation, markedly decreased the nuclear accumulation of 8-oxoG in microglia, and inhibited microgliosis and neuronal loss. Gene expression profiling revealed that MTH1 and OGG1 efficiently suppress progression of AD by inducing various protective genes against AD pathogenesis initiated by Aß/Tau accumulation in 3xTg-AD brain. Our findings indicate that efficient suppression of 8-oxoG accumulation in brain genomes is a new approach for prevention and treatment of AD.
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