ArticleCommunications biology2021
HMGB1 signaling phosphorylates Ku70 and impairs DNA damage repair in Alzheimer's disease pathology.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- High mobility group box 1 and its post-translational modifications: Molecular mechanisms underlying neurodegenerative disease pathogenesis.Neural regeneration research · 2026Article
- Targeting non-apoptotic regulated cell death (RCD) to treat neurodegenerative diseases.Acta pharmaceutica Sinica. B · 2026Review
- Unraveling the intersection of aging and Parkinson's disease: a collaborative roadmap for advancing research models.NPJ Parkinson's disease · 2026Review
- HMGB1 reduce DNA damage by binding KU70 to activate NHEJ pathway in colorectal cancer cells after radiation.PloS one · 2026Article
- Roles of chromatin and genome instability in cellular senescence and their relevance to ageing and related diseases.Nature reviews. Molecular cell biology · 2024Review
- Glycyrrhizin ameliorates colorectal cancer progression by regulating NHEJ pathway through inhibiting HMGB1-induced DNA damage response.Scientific reports · 2024Article
- PQBP3 prevents senescence by suppressing PSME3-mediated proteasomal Lamin B1 degradation.The EMBO journal · 2024Article
- Early oxidative stress and DNA damage in Aβ-burdened hippocampal neurons in an Alzheimer's-like transgenic rat model.Communications biology · 2024Article
- Dynamic molecular network analysis of iPSC-Purkinje cells differentiation delineates roles of ISG15 in SCA1 at the earliest stage.Communications biology · 2024Article
- Lupus autoantibodies initiate neuroinflammation sustained by continuous HMGB1:RAGE signaling and reversed by increased LAIR-1 expression.Nature immunology · 2024Article
- Necrosis Links Neurodegeneration and Neuroinflammation in Neurodegenerative Disease.International journal of molecular sciences · 2024Review
- Molecular cloning, subcellular localization, and rapid recruitment to DNA damage sites of chicken Ku70.Scientific reports · 2024Article
- Maintaining Genome Integrity: Protein Kinases and Phosphatases Orchestrate the Balancing Act of DNA Double-Strand Breaks Repair in Cancer.International journal of molecular sciences · 2023Review
- Prioritization of risk genes for Alzheimer's disease: an analysis framework using spatial and temporal gene expression data in the human brain based on support vector machine.Frontiers in genetics · 2023Article
- How neurons die in Alzheimer's disease: Implications for neuroinflammation.Current opinion in neurobiology · 2022Review
- Cis- and trans-resveratrol have opposite effects on histone serine-ADP-ribosylation and tyrosine induced neurodegeneration.Nature communications · 2022Article
- Discovery and validation of Ferroptosis-related molecular patterns and immune characteristics in Alzheimer's disease.Frontiers in aging neuroscience · 2022Article
- Interaction between autophagy and the NLRP3 inflammasome in Alzheimer's and Parkinson's disease.Frontiers in aging neuroscience · 2022Review
- Post-Translational Modification of HMGB1 Disulfide Bonds in Stimulating and Inhibiting Inflammation.Cells · 2021Review
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Authors and funding
21 authors at 6 institutions in 2 countries.
Funding
Abstract
DNA damage is increased in Alzheimer's disease (AD), while the underlying mechanisms are unknown. Here, we employ comprehensive phosphoproteome analysis, and identify abnormal phosphorylation of 70 kDa subunit of Ku antigen (Ku70) at Ser77/78, which prevents Ku70-DNA interaction, in human AD postmortem brains. The abnormal phosphorylation inhibits accumulation of Ku70 to the foci of DNA double strand break (DSB), impairs DNA damage repair and eventually causes transcriptional repression-induced atypical cell death (TRIAD). Cells under TRIAD necrosis reveal senescence phenotypes. Extracellular high mobility group box 1 (HMGB1) protein, which is released from necrotic or hyper-activated neurons in AD, binds to toll-like receptor 4 (TLR4) of neighboring neurons, and activates protein kinase C alpha (PKCα) that executes Ku70 phosphorylation at Ser77/78. Administration of human monoclonal anti-HMGB1 antibody to post-symptomatic AD model mice decreases neuronal DSBs, suppresses secondary TRIAD necrosis of neurons, prevents escalation of neurodegeneration, and ameliorates cognitive symptoms. TRIAD shares multiple features with senescence. These results discover the HMGB1-Ku70 axis that accounts for the increase of neuronal DNA damage and secondary enhancement of TRIAD, the cell death phenotype of senescence, in AD.
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