ReviewFrontiers in cellular neuroscience2014
The two-hit hypothesis for neuroinflammation: role of exogenous ATP in modulating inflammation in the brain.
Review in Frontiers in cellular neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 125 citations in OpenAlex.
- Metabolic Intervention with Dimethyl Malonate Impairs Phagocytic Clearance but Fails to Protect Neurons.bioRxiv : the preprint server for biology · 2026Article
- Navigating the maze of Alzheimer's: nimodipine and pioglitazone combination in the spotlight through inhibition of P2X7 dependent NLRP3 inflammasome activation.Inflammopharmacology · 2026Review
- Store-operated calcium entry drives alcohol-exacerbated neuroinflammation in retinal degeneration.Cell death discovery · 2026Article
- Ecto-5'-nucleotidase/CD73 reduces COX-2 expression in activated macrophages.Scientific reports · 2026Article
- Profile of NT-0527, a brain penetrant NLRP3 Inflammasome inhibitor suitable as anRSC medicinal chemistry · 2025Article
- Calcium Signaling in Astrocytes and Its Role in the Central Nervous System Injury.Molecular neurobiology · 2025Review
- Increased spinal adenosine after subacute cervical injury correlates with sustained upregulation of CD39 and CD73 in microglia.Neurochemistry international · 2025Article
- Microglial replacement in a Sandhoff disease mouse model reveals myeloid-derived β-hexosaminidase is necessary for neuronal health.Nature communications · 2025Article
- The role of maternal infections in neurodevelopmental psychiatric disorders: focus on the P2X7/NLRP3/IL-1β signalling pathway.Journal of neuroinflammation · 2025Review
- P2Y12 receptor-mediated cyclooxygenase 2 (COX-2) expression enhances tumor cell progression in a mouse model of lymphoma.Purinergic signalling · 2025Article
- Multi-Omics Analysis Reveals Disturbances of Purine Metabolism and Glutamate Metabolism in the Hippocampus of Lipopolysaccharide-Induced Mouse Model of Depression.Brain and behavior · 2025Article
- Mitochondria: the hidden engines of traumatic brain injury-driven neurodegeneration.Frontiers in cellular neuroscience · 2025Review
- Myeloid-derived β-hexosaminidase is essential for neuronal health and lysosome function: implications for Sandhoff disease.bioRxiv : the preprint server for biology · 2024Article
- Extracellular Purine Metabolism-Potential Target in Multiple Sclerosis.Molecular neurobiology · 2024Review
- Pannexin1 Channel-Mediated Inflammation in Acute Ischemic Stroke.Aging and disease · 2024Review
- Role and therapeutic targets of P2X7 receptors in neurodegenerative diseases.Frontiers in immunology · 2024Review
- Article
- Purinergic neurotransmission receptor P2X4 silencing alleviates intracerebral hemorrhage-induced neuroinflammation by blocking the NLRP1/Caspase-1 pathway.Scientific reports · 2023Article
- Machine learning discriminates P2X7-mediated intracellular calcium sparks in human-induced pluripotent stem cell-derived neural stem cells.Scientific reports · 2023Article
- Targeting purinergic receptors to attenuate inflammation of dry eye.Purinergic signalling · 2023Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain inflammation is a common occurrence following responses to varied insults such as bacterial infections, stroke, traumatic brain injury and neurodegenerative disorders. A common mediator for these varied inflammatory responses is prostaglandin E2 (PGE2), produced by the enzymatic activity of cyclooxygenases (COX) 1 and 2. Previous attempts to reduce neuronal inflammation through COX inhibition, by use of nonsteroidal anti-inflammatory drugs (NSAIDs), have met with limited success. We are proposing the two-hit model for neuronal injury-an initial localized inflammation mediated by PGE2 (first hit) and the simultaneous release of adenosine triphosphate (ATP) by injured cells (second hit), which significantly enhances the inflammatory response through increased synthesis of PGE2. Several evidences on the role of exogenous ATP in inflammation have been reported, including contrary instances where extracellular ATP reduces inflammatory events. In this review, we will examine the current literature on the role of P2 receptors, to which ATP binds, in modulating inflammatory reactions during neurodegeneration. Targeting the P2 receptors, therefore, provides a therapeutic alternative to reduce inflammation in the brain. P2 receptor-based anti-inflammatory drugs (PBAIDs) will retain the activities of essential COX enzymes, yet will significantly reduce neuroinflammation by decreasing the enhanced production of PGE2 by extracellular ATP.
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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.