ArticleGlia2014
Inhibition of UDP/P2Y6 purinergic signaling prevents phagocytosis of viable neurons by activated microglia in vitro and in vivo.
Article in Glia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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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.
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Who cites it
90 citing papers in PubMed, 143 citations in OpenAlex.
- Investigation of reported small molecule P2Y6 receptor antagonists.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- A Dopamine D1-Like Receptor Agonist Ameliorates Traumatic Brain Injury Through its Immunosuppressive Effects.Cellular and molecular neurobiology · 2026Article
- Microglia surveillance is directed toward neuron activation during sustained intracortical microstimulation.Journal of neural engineering · 2026Article
- TSC-associated microglial hyperactivity: enhanced calcium signaling, metabolism, and phagocytosis.Acta neuropathologica · 2026Article
- Article
- Microglial pathological synaptic pruning in epilepsy: pathophysiology and therapeutic potential.Frontiers in immunology · 2026Review
- Microglial phagocytosis in Alzheimer disease.Nature reviews. Neurology · 2026Review
- Article
- Adrenergic Control of P2Y6 Receptor-Dependent Phagocytosis in Rodent and Human Microglia.Glia · 2025Article
- Microglial purinergic signaling in Alzheimer's disease.Purinergic signalling · 2025Review
- Inhibition of P2Y6 Receptor-Mediated Microglia Phagocytosis Aggravates Brain Injury in Mice of Intracerebral Hemorrhage.Cellular and molecular neurobiology · 2025Article
- Dissecting surveying behavior of reactive microglia under chronic neurodegeneration.bioRxiv : the preprint server for biology · 2025Article
- Modification of Neural Circuit Functions by Microglial P2Y6 Receptors in Health and Neurodegeneration.Molecular neurobiology · 2025Review
- Pyrimidinergic P2Y1-Like Nucleotide Receptors Are Functional in Rat Conjunctival Goblet Cells.Investigative ophthalmology & visual science · 2025Article
- The microglial P2YTranslational neurodegeneration · 2024Review
- Microglial P2YNeuron · 2024Article
- Microglia phagocytic mechanisms: Development informing disease.Current opinion in neurobiology · 2024Review
- Stopping the aged brain from eating itself.Aging · 2024Article
- The endotoxin hypothesis of Alzheimer's disease.Molecular neurodegeneration · 2024Review
- Cell death by phagocytosis.Nature reviews. Immunology · 2024Review
30 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Microglia activated through Toll-like receptor (TLR)-2 or -4 can cause neuronal death by phagocytosing otherwise-viable neurons-a form of cell death called "phagoptosis." UDP release from neurons has been shown to provoke microglial phagocytosis of neurons via microglial P2Y6 receptors, but whether inhibition of this process affects neuronal survival is unknown. We tested here whether inhibition of P2Y6 signaling could prevent neuronal death in inflammatory conditions, and whether UDP signaling can induce phagoptosis of stressed but viable neurons. We find that delayed neuronal loss and death in mixed neuronal/glial cultures induced by the TLR ligands lipopolysaccharide (LPS) or lipoteichoic acid was prevented by: apyrase (to degrade nucleotides), Reactive Blue 2 (to inhibit purinergic signaling), or MRS2578 (to specifically block P2Y6 receptors). In each case, inflammatory activation of microglia was not affected, and the rescued neurons remained viable for at least 7 days. Blocking P2Y6 receptors with MRS2578 also prevented phagoptosis of neurons induced by 250 nM amyloid beta 1-42, 5 μM peroxynitrite, or 50 μM 3-morpholinosydnonimine (which releases reactive oxygen and nitrogen species). Furthermore, the P2Y6 receptor agonist UDP by itself was sufficient to stimulate microglial phagocytosis and to induce rapid neuronal loss that was prevented by eliminating microglia or inhibiting phagocytosis. In vivo, injection of LPS into rat striatum induced microglial activation and delayed neuronal loss and blocking P2Y6 receptors with MRS2578 prevented this neuronal loss. Thus, blocking UDP/P2Y6 signaling is sufficient to prevent neuronal loss and death induced by a wide range of stimuli that activate microglial phagocytosis of neurons.
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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.