ArticleCommunications biology2022
Failure of DNA double-strand break repair by tau mediates Alzheimer's disease pathology in vitro.
Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 44 citations in OpenAlex.
- Intranasal drug delivery to the brain for neurodegenerative diseases: Current efforts and challenges in delivery platforms and modeling.Advanced drug delivery reviews · 2026Review
- DREAM repressive activity links somatic mutation, lifespan and disease.Nature aging · 2026Article
- When R-Loops Go Awry: Genome Instability and Neurological Diseases.The European journal of neuroscience · 2026Review
- Implications of virus-induced stress granules in tauopathies.Translational neurodegeneration · 2026Review
- Drosophila wing is a high-throughput and versatile screening tool for Tau-mediated disease mechanisms and drug discovery.Disease models & mechanisms · 2026Article
- Post-translational modifications as a regulatory code for tau function in health and disease.Frontiers in dementia · 2026Review
- Review
- Subcellular functions of tau mediate repair response and synaptic homeostasis in injury.Molecular psychiatry · 2025Article
- Emerging roles for innate and adaptive immunity in tauopathies.Cell reports · 2025Review
- The DREAM complex links somatic mutation, lifespan, and disease.bioRxiv : the preprint server for biology · 2025Article
- The many connections of UFMylation with Alzheimer's disease: a comprehensive review.Molecular neurodegeneration · 2025Review
- Diverse influences on tau aggregation and implications for disease progression.Genes & development · 2025Review
- A reciprocal relationship between markers of genomic DNA damage and alpha-synuclein pathology in dementia with Lewy bodies.Molecular neurodegeneration · 2025Article
- The UFMylation pathway is impaired in Alzheimer's disease.Molecular neurodegeneration · 2024Article
- Proteins Associated with Neurodegenerative Diseases: Link to DNA Repair.Biomedicines · 2024Review
- Inflammation and DNA methylation in Alzheimer's disease: mechanisms of epigenetic remodelling by immune cell oxidants in the ageing brain.Redox report : communications in free radical research · 2024Review
- Updates in Alzheimer's disease: from basic research to diagnosis and therapies.Translational neurodegeneration · 2024Review
- Tau beyond Tangles: DNA Damage Response and Cytoskeletal Protein Crosstalk on Neurodegeneration.International journal of molecular sciences · 2024Review
- Adaptive and Maladaptive DNA Breaks in Neuronal Physiology and Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Introducing the Role of Genotoxicity in Neurodegenerative Diseases and Neuropsychiatric Disorders.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA double-strand break (DSB) is the most severe form of DNA damage and accumulates with age, in which cytoskeletal proteins are polymerized to repair DSB in dividing cells. Since tau is a microtubule-associated protein, we investigate whether DSB is involved in tau pathologies in Alzheimer's disease (AD). First, immunohistochemistry reveals the frequent coexistence of DSB and phosphorylated tau in the cortex of AD patients. In vitro studies using primary mouse cortical neurons show that non-p-tau accumulates perinuclearly together with the tubulin after DSB induction with etoposide, followed by the accumulation of phosphorylated tau. Moreover, the knockdown of endogenous tau exacerbates DSB in neurons, suggesting the protective role of tau on DNA repair. Interestingly, synergistic exposure of neurons to microtubule disassembly and the DSB strikingly augments aberrant p-tau aggregation and apoptosis. These data suggest that DSB plays a pivotal role in AD-tau pathology and that the failure of DSB repair leads to tauopathy.
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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.