ArticleJournal of neuroinflammation2018
A central role for P2X7 receptors in human microglia.
Article in Journal of neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 109 citations in OpenAlex.
- P2X7 receptor-mediated IL-1β release by human brain tissue: the impact of CNS-penetrant potential therapeutics.Brain : a journal of neurology · 2026Article
- NEMO (IKKγ) citrullination in microglia promotes neuroinflammation in the post-ischemic brain.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Formononetin Attenuates Seizure Severity and Cognitive Deficits in PTZ-Kindled Rats with Associated Changes in Oxidative Stress and P2 X 7/IL-1β/Glutamate Signalling Markers.Neurochemical research · 2026Article
- Altered Pannexin2 Expression in Retinal Degeneration: Insights from the P23H Mouse Model of Retinis Pigmentosa.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- A Holistic Approach to Identifying a Positron Emission Tomography (PET) Tracer Candidate for In Vivo Imaging of Purinergic P2X7 Receptor in Neuroinflammation.ACS pharmacology & translational science · 2026Article
- Deficiency of Tissue Nonspecific Alkaline Phosphatase Dysregulates Microglial Morphology and Function in a Mouse Model of Infantile Hypophosphatasia.Journal of neurochemistry · 2026Article
- Affinity-guided labeling reveals P2X7 nanoscale membrane redistribution during BV2 microglial activation.eLife · 2026Article
- Focusing on inflammation-driven pyroptosis in postherpetic neuralgia: from molecular mechanisms to therapeutic strategies.Frontiers in immunology · 2026Review
- P2X7 Receptor in Rare Diseases: Shared Molecular Mechanisms and Therapeutic Implications.Journal of inflammation research · 2026Review
- P2X7 receptor-dependent microglia-astrocyte coupling in Alzheimer's disease: from eATP sensing to synaptic and proteostatic failure.Frontiers in aging neuroscience · 2026Review
- Purinergic and extracellular vesicle signaling in alcohol-induced blood-brain barrier breakdown and neuroimmune activation.Brain, behavior, and immunity · 2025Review
- P2RX7 modulates the function of human microglia-like cells and mediates the association of IL18 with Alzheimer's disease traits.Neurobiology of disease · 2025Article
- Bidirectional Interplay Between Microglia and Mast Cells.International journal of molecular sciences · 2025Review
- The Multifaceted Role of P2X7R in Microglia and Astrocytes.Neurochemical research · 2025Review
- Extracellular ATP regulates phagocytic activity, mitochondrial respiration, and cytokine secretion of human astrocytic cells.Purinergic signalling · 2025Article
- New insights into pathogenisis and therapies of P2X7R in Parkinson's disease.NPJ Parkinson's disease · 2025Review
- cGAMP promotes inner blood-retinal barrier breakdown through P2RX7-mediated transportation into microglia.Journal of neuroinflammation · 2025Article
- Priming and release of cytokine IL-1β in microglial cells from the retina.Experimental eye research · 2025Article
- Comprehensive insights into potential roles of purinergic P2 receptors on diseases: Signaling pathways involved and potential therapeutics.Journal of advanced research · 2025Review
- Partners in health and disease: pineal gland and purinergic signalling.Purinergic signalling · 2025Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe ATP-gated ionotropic P2X7 receptor (P2X7R) has the unusual ability to function as a small cation channel and a trigger for permeabilization of plasmalemmal membranes. In murine microglia, P2X7R-mediated permeabilization is fundamental to microglial activation, proliferation, and IL-1β release. However, the role of the P2X7R in primary adult human microglia is poorly understood.
methodsWe used patch-clamp electrophysiology to record ATP-gated current in cultured primary human microglia; confocal microscopy to measure membrane blebbing; fluorescence microscopy to demonstrate membrane permeabilization, caspase-1 activation, phosphatidylserine translocation, and phagocytosis; and kit-based assays to measure cytokine levels.
resultsWe found that ATP-gated inward currents facilitated with repetitive applications of ATP as expected for current through P2X7Rs and that P2X7R antagonists inhibited these currents. P2X7R antagonists also prevented the ATP-induced uptake of large cationic fluorescent dyes whereas drugs that target pannexin-1 channels had no effect. In contrast, ATP did not induce uptake of anionic dyes. The uptake of cationic dyes was blocked by drugs that target Cl
conclusionsOur results demonstrate that primary human microglia in culture express functional P2X7Rs that stimulate both ATP-gated cationic currents and uptake of large molecular weight cationic dyes. Importantly, our data demonstrate that hypotheses drawn from work on murine immune cells accurately predict the essential role of P2X7Rs in a number of human innate immune functions such as phagocytosis and caspase-1 activation. Therefore, the P2X7R represents an attractive target for therapeutic intervention in human neuroinflammatory disorders.
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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.