ArticleF1000Research2013
Extracellular histone H1 is neurotoxic and drives a pro-inflammatory response in microglia.
Article in F1000Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 159 citations in OpenAlex.
- Role of post-translational modifications in modulating histone reactivity in the extracellular environment.Biochemical Society transactions · 2026Review
- Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones.Materials today. Bio · 2026Review
- Regulation of histones in thromboinflammation.Frontiers in immunology · 2026Review
- Blood gene expression network expression strongly relates to brain amyloid burden.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Age-dependent brain responses to mechanical stress determine resilience in a chronic lymphatic drainage impairment model.The Journal of clinical investigation · 2025Article
- Extracellular Histones as Exosome Membrane Proteins Regulated by Cell Stress.Journal of extracellular vesicles · 2025Article
- Increased cell-free DNA in CSF and serum of hip fracture patients with delirium.Brain communications · 2025Article
- Fantastic proteins and where to find them - histones, in the nucleus and beyond.Journal of cell science · 2024Review
- Proteome characterization of extracellular vesicles from human milk: Uncovering the surfaceome by a lipid-based protein immobilization technology.Journal of extracellular biology · 2024Article
- Extracellular mixed histones are neurotoxic and modulate select neuroimmune responses of glial cells.PloS one · 2024Article
- Neutrophil Extracellular Traps in Cerebral Ischemia/Reperfusion Injury: Friend and Foe.Current neuropharmacology · 2023Review
- Histone-stimulated platelet adhesion to mouse cremaster venules in vivo is dependent on von Willebrand factor.Microcirculation (New York, N.Y. : 1994) · 2022Article
- Circulating extracellular histones exacerbate acute lung injury by augmenting pulmonary endothelial dysfunction via TLR4-dependent mechanism.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Extra-nuclear histones: origin, significance and perspectives.Molecular and cellular biochemistry · 2022Review
- Roles of the Exosomes Derived From Myeloid-Derived Suppressor Cells in Tumor Immunity and Cancer Progression.Frontiers in immunology · 2022Review
- Extracellular Nucleosomes Accelerate Microglial InflammationFrontiers in immunology · 2022Article
- Neutrophil Extracellular Traps Exacerbate Ischemic Brain Damage.Molecular neurobiology · 2022Review
- Multi-Omics Analysis Reveals the Systematic Relationship Between Oral Homeostasis and Chronic Sleep Deprivation in Rats.Frontiers in immunology · 2022Article
- Melatonin and Microglia.International journal of molecular sciences · 2021Review
- Intrabronchial application of extracellular histones shows no proinflammatory effects in swine in a translational pilot study.BMC research notes · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
In neurodegenerative conditions and following brain trauma it is not understood why neurons die while astrocytes and microglia survive and adopt pro-inflammatory phenotypes. We show here that the damaged adult brain releases diffusible factors that can kill cortical neurons and we have identified histone H1 as a major extracellular candidate that causes neurotoxicity and activation of the innate immune system. Extracellular core histones H2A, H2B H3 and H4 were not neurotoxic. Innate immunity in the central nervous system is mediated through microglial cells and we show here for the first time that histone H1 promotes their survival, up-regulates MHC class II antigen expression and is a powerful microglial chemoattractant. We propose that when the central nervous system is degenerating, histone H1 drives a positive feedback loop that drives further degeneration and activation of immune defences which can themselves be damaging. We suggest that histone H1 acts as an antimicrobial peptide and kills neurons through mitochondrial damage and apoptosis.
Identifiers
What OpenQuestion holds
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.