ArticleNucleic acids research2022
Persistent DNA damage associated with ATM kinase deficiency promotes microglial dysfunction.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The trial behind it
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Sublethal Caspase-8 Activation Drives Radiation-Induced Genetic Instability and Oncogenic Transformation Through Endonuclease G and Non-Canonical NF-κB Signaling.International journal of molecular sciences · 2026Article
- Recent Advances in Therapy for the Neurodegenerative Disorder Ataxia-Telangiectasia.International journal of molecular sciences · 2026Review
- Microglial Adaptations to Chronic Nicotine in the Cerebellum: Proteomic Evidence for Neuroimmune Vulnerability.Journal of proteome research · 2026Article
- ATM interaction with GRP94 modulates oncogenic receptor expression and signaling and microglial activation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Population Pharmacokinetic Modeling and Pediatric Exposure of Dexamethasone Sodium Phosphate Encapsulated in Erythrocytes (eDSP) Administered Monthly for Treatment of Neurological Symptoms of Patients With Ataxia Telangiectasia.CPT: pharmacometrics & systems pharmacology · 2025Article
- Neurological Complications in Inborn Errors of Immunity: A Scoping Review of Clinical Spectrum, Pathophysiological Mechanisms, and Therapeutic Strategies.Clinical reviews in allergy & immunology · 2025Article
- Modulating neuroinflammation and cognitive function in postoperative cognitive dysfunction via CCR5-GPCRs-Ras-MAPK pathway targeting with microglial EVs.CNS neuroscience & therapeutics · 2024Article
- ATM inhibition enhance immunotherapy by activating STING signaling and augmenting MHC Class I.Cell death & disease · 2024Article
- Microglia-derived extracellular vesicles trigger age-related neurodegeneration upon DNA damage.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Disproportionate Expression of ATM in Cerebellar Cortex During Human Neurodevelopment.Cerebellum (London, England) · 2024Article
- Regulation of transcription patterns, poly(ADP-ribose), and RNA-DNA hybrids by the ATM protein kinase.Cell reports · 2024Article
- A-T neurodegeneration and DNA damage-induced transcriptional stress.DNA repair · 2024Review
- Emerging role of senescent microglia in brain aging-related neurodegenerative diseases.Translational neurodegeneration · 2024Review
- cGAS-STING signalling regulates microglial chemotaxis in genome instability.Nucleic acids research · 2024Article
- Cell death by phagocytosis.Nature reviews. Immunology · 2024Review
- ATM-deficiency-induced microglial activation promotes neurodegeneration in ataxia-telangiectasia.Cell reports · 2024Article
- Regulation of transcription patterns, poly-ADP-ribose, and RNA-DNA hybrids by the ATM protein kinase.bioRxiv : the preprint server for biology · 2023Article
- Inhibition of ATM-directed antiviral responses by HIV-1 Vif.PLoS pathogens · 2023Article
- DNA Damage-Mediated Neurotoxicity in Parkinson's Disease.International journal of molecular sciences · 2023Review
- Interrogation of human microglial phagocytosis by CRISPR genome editing.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The autosomal recessive genome instability disorder Ataxia-telangiectasia, caused by mutations in ATM kinase, is characterized by the progressive loss of cerebellar neurons. We find that DNA damage associated with ATM loss results in dysfunctional behaviour of human microglia, immune cells of the central nervous system. Microglial dysfunction is mediated by the pro-inflammatory RELB/p52 non-canonical NF-κB transcriptional pathway and leads to excessive phagocytic clearance of neuronal material. Activation of the RELB/p52 pathway in ATM-deficient microglia is driven by persistent DNA damage and is dependent on the NIK kinase. Activation of non-canonical NF-κB signalling is also observed in cerebellar microglia of individuals with Ataxia-telangiectasia. These results provide insights into the underlying mechanisms of aberrant microglial behaviour in ATM deficiency, potentially contributing to neurodegeneration in Ataxia-telangiectasia.
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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.