ArticleThe Journal of biological chemistry2012
Sublethal doses of β-amyloid peptide abrogate DNA-dependent protein kinase activity.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
34 citing papers in PubMed, 54 citations in OpenAlex.
- Loss of DNA-PK complex in recurrent pterygium suggests a role for defective double-strand break repair.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Article
- Proteins Associated with Neurodegenerative Diseases: Link to DNA Repair.Biomedicines · 2024Review
- Extrachromosomal DNA: Molecular perspectives in aging and neurodegenerative diseases.Intractable & rare diseases research · 2024Article
- The DNA repair protein DNA-PKcs modulates synaptic plasticity via PSD-95 phosphorylation and stability.EMBO reports · 2024Article
- Neurotoxic β-amyloid oligomers cause mitochondrial dysfunction-the trigger for PANoptosis in neurons.Frontiers in aging neuroscience · 2024Review
- Review
- Sting and p53 DNA repair pathways are compromised in Alzheimer's disease.Scientific reports · 2023Article
- Activated or Impaired: An Overview of DNA Repair in Neurodegenerative Diseases.Aging and disease · 2022Article
- DNA Double-Strand Breaks as Pathogenic Lesions in Neurological Disorders.International journal of molecular sciences · 2022Review
- DNA repair protein DNA-PK protects PC12 cells from oxidative stress-induced apoptosis involving AKT phosphorylation.Molecular biology reports · 2022Article
- The Role of DNA Damage in Neural Plasticity in Physiology and Neurodegeneration.Frontiers in cellular neuroscience · 2022Review
- Cellular functions of the protein kinase ATM and their relevance to human disease.Nature reviews. Molecular cell biology · 2021Review
- Crosstalk between Different DNA Repair Pathways Contributes to Neurodegenerative Diseases.Biology · 2021Review
- Tau and DNA Damage in Neurodegeneration.Brain sciences · 2020Review
- Genistein and Galantamine Combinations Decrease β-Amyloid PeptideNeurotoxicity research · 2020Article
- Contributions of DNA Damage to Alzheimer's Disease.International journal of molecular sciences · 2020Review
- Neuroprotection against Amyloid-Neural plasticity · 2020Article
- Integrating Gene and Protein Expression Reveals Perturbed Functional Networks in Alzheimer's Disease.Cell reports · 2019Article
- Structure of amyloid βScientific reports · 2019Article
- Aging Neurovascular Unit and Potential Role of DNA Damage and Repair in Combating Vascular and Neurodegenerative Disorders.Frontiers in neuroscience · 2019Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulation of DNA damage and deficiency in DNA repair potentially contribute to the progressive neuronal loss in neurodegenerative disorders, including Alzheimer disease (AD). In multicellular eukaryotes, double strand breaks (DSBs), the most lethal form of DNA damage, are mainly repaired by the nonhomologous end joining pathway, which relies on DNA-PK complex activity. Both the presence of DSBs and a decreased end joining activity have been reported in AD brains, but the molecular player causing DNA repair dysfunction is still undetermined. β-Amyloid (Aβ), a potential proximate effector of neurotoxicity in AD, might exert cytotoxic effects by reactive oxygen species generation and oxidative stress induction, which may then cause DNA damage. Here, we show that in PC12 cells sublethal concentrations of aggregated Aβ(25-35) inhibit DNA-PK kinase activity, compromising DSB repair and sensitizing cells to nonlethal oxidative injury. The inhibition of DNA-PK activity is associated with down-regulation of the catalytic subunit DNA-PK (DNA-PKcs) protein levels, caused by oxidative stress and reversed by antioxidant treatment. Moreover, we show that sublethal doses of Aβ(1-42) oligomers enter the nucleus of PC12 cells, accumulate as insoluble oligomeric species, and reduce DNA-PK kinase activity, although in the absence of oxidative stress. Overall, these findings suggest that Aβ mediates inhibition of the DNA-PK-dependent nonhomologous end joining pathway contributing to the accumulation of DSBs that, if not efficiently repaired, may lead to the neuronal loss observed in AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.