ArticleHuman molecular genetics2010
A DNA damage-activated checkpoint kinase phosphorylates tau and enhances tau-induced neurodegeneration.
Article in Human molecular genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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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
40 citing papers in PubMed, 71 citations in OpenAlex.
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- Implications of virus-induced stress granules in tauopathies.Translational neurodegeneration · 2026Review
- Molecular Mechanisms of EDC-Induced Alzheimer's Disease and of Traditional Chinese Medicine Active Substances in Treating AD and Antagonizing EDC-Induced Effects.Neurochemical research · 2025Article
- The many connections of UFMylation with Alzheimer's disease: a comprehensive review.Molecular neurodegeneration · 2025Review
- Uncovering Cell Cycle Dysregulations and Associated Mechanisms in Cancer and Neurodegenerative Disorders: A Glimpse of Hope for Repurposed Drugs.Molecular neurobiology · 2024Review
- 9-Methylfascaplysin Prevents Neuroinflammation and Synaptic Damage via Cell-Specific Inhibition of Kinases in APP/PS1 Transgenic Mice.CNS neuroscience & therapeutics · 2024Article
- Tau is required for glial lipid droplet formation and resistance to neuronal oxidative stress.Nature neuroscience · 2024Article
- Investigation into the Neuroprotective and Therapeutic Potential of Plant-Derived Chk2 Inhibitors.International journal of molecular sciences · 2024Review
- Evidence that Alzheimer's Disease Is a Disease of Competitive Synaptic Plasticity Gone Awry.Journal of Alzheimer's disease : JAD · 2024Review
- DNA Damage Response-Associated Cell Cycle Re-Entry and Neuronal Senescence in Brain Aging and Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2023Review
- Failure of DNA double-strand break repair by tau mediates Alzheimer's disease pathology in vitro.Communications biology · 2022Article
- Non-Rodent Genetic Animal Models for Studying Tauopathy: Review ofInternational journal of molecular sciences · 2021Review
- Microtubule affinity-regulating kinase 4 with an Alzheimer's disease-related mutation promotes tau accumulation and exacerbates neurodegeneration.The Journal of biological chemistry · 2020Article
- Tau and DNA Damage in Neurodegeneration.Brain sciences · 2020Review
- Emerging Evidences for an Implication of the Neurodegeneration-Associated Protein TAU in Cancer.Brain sciences · 2020Review
- Tau affects P53 function and cell fate during the DNA damage response.Communications biology · 2020Article
- Tau Abnormalities and Autophagic Defects in Neurodegenerative Disorders; A Feed-forward Cycle.Galen medical journal · 2020Review
- DNA repair deficiency and senescence in concussed professional athletes involved in contact sports.Acta neuropathologica communications · 2019Article
- Molecular Targets in Alzheimer's Disease.Molecular neurobiology · 2019Review
- Heterochromatic genome instability and neurodegeneration sharing similarities with Alzheimer's disease in old Bmi1+/- mice.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Hyperphosphorylation of the microtubule associated protein tau is detected in the brains of individuals with a range of neurodegenerative diseases including Alzheimer's disease (AD). An imbalance in phosphorylation and/or dephosphorylation of tau at disease-related sites has been suggested to initiate the abnormal metabolism and toxicity of tau in disease pathogenesis. However, the mechanisms underlying abnormal phosphorylation of tau in AD are not fully understood. Here, we show that the DNA damage-activated Checkpoint kinase 2 (Chk2) is a novel tau kinase and enhances tau toxicity in a transgenic Drosophila model. Overexpression of Drosophila Chk2 increases tau phosphorylation at Ser262 and enhances tau-induced neurodegeneration in transgenic flies expressing human tau. The non-phosphorylatable Ser262Ala mutation abolishes Chk2-induced enhancement of tau toxicity, suggesting that the Ser262 phosphorylation site is involved in the enhancement of tau toxicity by Chk2. In vitro kinase assays revealed that human Chk2 and a closely related checkpoint kinase 1 (Chk1) directly phosphorylate human tau at Ser262. We also demonstrate that Drosophila Chk2 does not modulate the activity of the fly homolog of microtubule affinity regulating kinase, which has been shown to be a physiological tau Ser262 kinase. Since accumulation of DNA damage has been detected in the brains of AD patients, our results suggest that the DNA damage-activated kinases Chk1 and Chk2 may be involved in tau phosphorylation and toxicity in the pathogenesis of 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.