P2X7 receptor: an emerging target in central nervous system diseases

Sperlágh, Beáta; Illes, Peter

doi:10.1016/j.tips.2014.08.002

Cited by 396Adenosine and Purinergic SignalingPain Mechanisms and TreatmentsTraumatic Brain Injury and Neurovascular Disturbances

P2X7 receptor: an emerging target in central nervous system diseases

Sperlágh, Beáta, Illes, Peter·2014·Trends in Pharmacological Sciences

DOI 10.1016/j.tips.2014.08.002

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Abstract

The ATP-sensitive homomeric P2X7 receptor (P2X7R) has received particular attention as a potential drug target because of its widespread involvement in inflammatory diseases as a key regulatory element of the inflammasome complex. However, it has only recently become evident that P2X7Rs also play a pivotal role in central nervous system (CNS) pathology. There is an explosion of data indicating that genetic deletion and pharmacological blockade of P2X7Rs alter responsiveness in animal models of neurological disorders, such as stroke, neurotrauma, epilepsy, neuropathic pain, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Parkinson's disease, and Huntington's disease. Moreover, recent studies suggest that P2X7Rs regulate the pathophysiology of psychiatric disorders, including mood disorders, implicating P2X7Rs as drug targets in a variety of CNS pathology.

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Activation of P2X7 receptors induced by viral infection leads to molecular alterations (neuroimmune response activation, ROS formation, and glutamate release), behavioral alterations, and mental disorders.
“their activation induced by viral infection leads to molecular (mainly neuroimmune response activation, reactive oxygen species (ROS) formation, and glutamate release) and behavioral alterations [17, 20] as well as to mental disorders [21].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [21]
P2X7 receptor activation increases neuroinflammatory responses, which have been associated with neurodegenerative diseases, psychiatric disorders and stroke.
“Remarkably, P2X7 receptor activation increases neuroinflammatory responses, which have been associated with neurodegenerative diseases, psychiatric disorders and stroke [21, 92–95], as further discussed.”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [21]
Purinergic signaling is involved in several psychiatric disorders, including MDD.
“Purinergic signaling is involved in several psychiatric disorders, including MDD [25,26,27,28], and is mediated by nucleoside and nucleotide actions on P1 (P1R) and P2 (P2R) receptors.”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [28]
P2X7R-mediated effects, mainly through activation of the neuroinflammatory response, have been involved in MDD, neurodegenerative diseases, schizophrenia, epilepsy, neuropathic pain, and brain injury.
“P2X7R-mediated effects, which mainly occurs through activation of the neuroinflammatory response, have been involved in MDD, neurodegenerative diseases, schizophrenia, epilepsy, neuropathic pain and brain injury [28,66,67,68].”
From P2X7 Receptor Signaling in Stress and Depression (2019) · cites this paper as [28]

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A comparative analysis of the activity of ligands acting at P2X and P2Y receptor subtypes in models of neuropathic, acute and inflammatory pain
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Adaptive phenotype of microglial cells during the normal postnatal development of the somatosensory “Barrel” cortex
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P2X7 Is a Scavenger Receptor for Apoptotic Cells in the Absence of Its Ligand, Extracellular ATP
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Synaptic localization of P2X7 receptors in the rat retina
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P2RX7 gene is associated consistently with mood disorders and predicts clinical outcome in three clinical cohorts
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ATP and the purine type 2 X7 receptor affect sleep
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Alteration of purinergic P2X4 and P2X7 receptor expression in rats with temporal-lobe epilepsy induced by pilocarpine
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The food dye FD&C Blue No. 1 is a selective inhibitor of the ATP release channel Panx1
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PKC-dependent ERK phosphorylation is essential for P2X7 receptor-mediated neuronal differentiation of neural progenitor cells
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Rodent Cortical Astroglia Express In Situ Functional P2X7 Receptors Sensing Pathologically High ATP Concentrations
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Combating innate inflammation: a new paradigm for acute treatment of stroke?
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Differential co-localisation of the P2X7 receptor subunit with vesicular glutamate transporters VGLUT1 and VGLUT2 in rat CNS
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P2X7 Receptor Antagonism Inhibits p38 Mitogen-Activated Protein Kinase Activation and Ameliorates Neuronal Apoptosis After Subarachnoid Hemorrhage in Rats
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Is pannexin the pore associated with the P2X7 receptor?
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Clemastine Potentiates the Human P2X7 Receptor by Sensitizing It to Lower ATP Concentrations
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Gain-of-function of P2X7 receptor gene variants in multiple sclerosis
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P2X 7 Receptor Activation Mediates Retinal Ganglion Cell Death in a Human Retina Model of Ischemic Neurodegeneration
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K+depolarization evokes ATP, adenosine and glutamate release from glia in rat hippocampus: a microelectrode biosensor study
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Splice-variants of the P2X7 receptor reveal differential agonist-dependence and functional coupling with pannexin-1
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P2X7pre‐synaptic receptors in adult rat cerebrocortical nerve terminals: a role in ATP‐induced glutamate release
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P2X7 receptors at adult neural progenitor cells of the mouse subventricular zone
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P2X4 receptors interact with both P2X2 and P2X7 receptors in the form of homotrimers
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P2X receptor antagonists for pain management: examination of binding and physicochemical properties
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P2X7 Antagonists as Potential Therapeutic Agents for the Treatment of CNS Disorders
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Mitochondrial dysfunction is involved in P2X7 receptor‐mediated neuronal cell death
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Contribution of Pannexin1 to Experimental Autoimmune Encephalomyelitis
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P2X7 receptor regulates leukocyte infiltrations in rat frontoparietal cortex following status epilepticus
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The Specificity Protein Factor Sp1 Mediates Transcriptional Regulation of P2X7 Receptors in the Nervous System
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Downregulation of P2X7receptor expression in rat oligodendrocyte precursor cells after hypoxia ischemia
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Dual Gating Mechanism and Function of P2X7 Receptor Channels
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Astrocyte–neuron interaction in the substantia gelatinosa of the spinal cord dorsal horn via P2X7 receptor‐mediated release of glutamate and reactive oxygen species
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ATP-P2X7 Receptor Modulates Axon Initial Segment Composition and Function in Physiological Conditions and Brain Injury
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Connexin hemichannel and pannexin channel electrophysiology: How do they differ?
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P2X7 receptor‐induced death of motor neurons by a peroxynitrite/ FAS ‐dependent pathway
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The role of purinergic signaling in depressive disorders.
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Alternative Splicing of the N-Terminal Cytosolic and Transmembrane Domains of P2X7 Controls Gating of the Ion Channel by ADP-Ribosylation
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Central sensitization of nociceptive neurons in rat medullary dorsal horn involves purinergic P2X7 receptors
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P2X7 Receptors Trigger ATP Exocytosis and Modify Secretory Vesicle Dynamics in Neuroblastoma Cells
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Residues 155 and 348 Contribute to the Determination of P2X7 Receptor Function via Distinct Mechanisms Revealed by Single-nucleotide Polymorphisms
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Variation in P2RX7 candidate gene (rs2230912) is not associated with bipolar I disorder and unipolar major depression in four European samples
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P2X receptors as targets for the treatment of status epilepticus
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Involvement of RVM-expressed P2X7 receptor in bone cancer pain: Mechanism of descending facilitation
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ATP‐P2X7receptor signaling controls basal and TNFα‐stimulated glial cell proliferation
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Electrophysiological classification of P2X7 receptors in rat cultured neocortical astroglia
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P2X7 Receptors in Satellite Glial Cells Mediate High Functional Expression of P2X3 Receptors in Immature Dorsal Root Ganglion Neurons
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Cognitive manic symptoms associated with the P2RX7 gene in bipolar disorder
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Lack of neuroprotection in the absence of P2X7 receptors in toxin-induced animal models of Parkinson's disease
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Activation of Trimeric P2X2 Receptors by Fewer than Three ATP Molecules
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The P2 Receptor Antagonist PPADS Supports Recovery from Experimental Stroke In Vivo
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Effect of genetic deletion and pharmacological antagonism of P2X7 receptors in a mouse animal model of migraine
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Receptor localization, native tissue binding and ex vivo occupancy for centrally penetrant P2X7 antagonists in the rat
Able, S., Fish, R., Bye, H., Booth, L. A., Logan, Y. R., Nathaniel, C., Hayter, P. M., & KATUGAMPOLA, S. D. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.01025.x · Cited by 47 · see citing works
Modulation/physiology of calcium channel sub-types in neurosecretory terminals
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The P2X7‐Egr pathway regulates nucleotide‐dependent inflammatory gene expression in microglia
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P2RX7 polymorphisms Gln460Arg and His155Tyr are not associated with major depressive disorder or remission after SSRI or ECT
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P2X7 receptor activation ameliorates CA3 neuronal damage via a tumor necrosis factor-α-mediated pathway in the rat hippocampus following status epilepticus
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ALS: Focus on purinergic signalling
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Synaptic terminals from mice midbrain exhibit functional P2X7 receptor
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Block of P2X7 receptors could partly reverse the delayed neuronal death in area CA1 of the hippocampus after transient global cerebral ischemia
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Potentiation of Inhibitory Synaptic Transmission by Extracellular ATP in Rat Suprachiasmatic Nuclei
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Blockade of P2X receptor prevents astroglial death in the dentate gyrus following pilocarpine-induced status epilepticus
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The phenothiazine-class antipsychotic drugs prochlorperazine and trifluoperazine are potent allosteric modulators of the human P2X7 receptor
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Discovery of 2-chloro-N-((4,4-difluoro-1-hydroxycyclohexyl)methyl)-5-(5-fluoropyrimidin-2-yl)benzamide as a potent and CNS penetrable P2X7 receptor antagonist
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A reassessment of P2X7 receptor inhibition as a neuroprotective strategy in rat models of contusion injury
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Purinergic signalling at the plasma membrane: a multipurpose and multidirectional mode to deal with amyotrophic lateral sclerosis and multiple sclerosis
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P2X7 receptors enhance glutamate release in hippocampal hilar neurons
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The Second Transmembrane Domain of P2X7 Contributes to Dilated Pore Formation
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Peripheral origin of IL-1β production in the rodent hippocampus under in vivo systemic bacterial lipopolysaccharide (LPS) challenge and its regulation by P2X7 receptors
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Mechanisms of protein kinase D activation in response to P2Y2and P2X7 receptors in primary astrocytes
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Synthesis and biological activity of a series of tetrasubstituted-imidazoles as P2X7 antagonists
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Temporal expression of P2X7 purinergic receptor during the course of experimental autoimmune encephalomyelitis
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Differential effects of undernourishment on the differentiation and maturation of rat enteric neurons
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P2X7 receptor in the trigeminal sensory nuclear complex contributes to tactile allodynia/hyperalgesia following trigeminal nerve injury
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P2X7 receptors regulate engulfing activity of non-stimulated resting astrocytes
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Dynamic micro-organization of P2X7 receptors revealed by PALM based single particle tracking
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Variation in the purinergic P2RX7 receptor gene and schizophrenia
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Natural compounds with P2X7 receptor-modulating properties
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Identification of 2-oxo-N-(phenylmethyl)-4-imidazolidinecarboxamide antagonists of the P2X7 receptor
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The P2X7 receptor as a route for non‐exocytotic glutamate release: dependence on the carboxyl tail
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Calmidazolium selectively inhibits exocytotic glutamate release evoked by P2X7 receptor activation
Cervetto, C., Mazzotta, M. C., Frattaroli, D., Alloisio, S., Nobile, M., Maura, G., & Marcoli, M. (2012) · Neurochemistry International · doi:10.1016/j.neuint.2012.02.034 · Cited by 29 · see citing works
Chronic stress induces prolonged suppression of the P2X7 receptor within multiple regions of the hippocampus: A cumulative threshold spectra analysis
Kongsui, R., Beynon, S. B., Johnson, S. J., Mayhew, J., Kuter, P., Nilsson, M., & Walker, F. R. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.05.017 · Cited by 29 · see citing works
Synthesis and structure–activity relationships of a series of (1H-pyrazol-4-yl)acetamide antagonists of the P2X7 receptor
Chambers, L. J., Stevens, A. J., Moses, A. P., Michel, A. D., Walter, D. S., Davies, D. J., Livermore, D. G., Fonfría, E., Demont, E. H., Vimal, M., et al. (2010) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2010.03.096 · Cited by 29 · see citing works
Activity and metabolism-related Ca2+ and mitochondrial dynamics in co-cultured human fetal cortical neurons and astrocytes
Fu, W., Ruangkittisakul, A., MacTavish, D., Baker, G. B., Ballanyi, K., & Jhamandas, J. H. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.07.029 · Cited by 28 · see citing works
Purinergic responses of calcium-dependent signaling pathways in cultured adult human astrocytes
Hashioka, S., Wang, Y. F., Little, J. P., Choi, H. B., Klegeris, A., McGeer, P. L., & McLarnon, J. G. (2014) · BMC Neuroscience · doi:10.1186/1471-2202-15-18 · Cited by 27 · see citing works
Structure–activity relationships and in vivo activity of (1H-pyrazol-4-yl)acetamide antagonists of the P2X7 receptor
Beswick, P., Billinton, A., Chambers, L. J., Dean, D. K., Fonfría, E., Gleave, R. J., Medhurst, S. J., Michel, A. D., Moses, A. P., Patel, S., et al. (2010) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2010.05.107 · Cited by 27 · see citing works
The effect of P2X7 receptor activation on nuclear factor‐kappa B phosphorylation induced by status epilepticus in the rat hippocampus
Kim, J., Kim, D., Ryu, H. J., Kim, W. I., Kim, M., Kim, D. W., Choi, S. Y., & Kang, T. (2013) · Hippocampus · doi:10.1002/hipo.22109 · Cited by 26 · see citing works
Potentiation of the glutamatergic synaptic input to rat locus coeruleus neurons by P2X7 receptors
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Discovery, synthesis and SAR of azinyl- and azolylbenzamides antagonists of the P2X7 receptor
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Evidence for two conductive pathways in P2X7 receptor: differences in modulation and selectivity
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Purinergic signaling in the cerebellum: Bergmann glial cells express functional ionotropic P2X7 receptors
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Up-regulation of P2X7 receptor-immunoreactivity by in vitro ischemia on the plasma membrane of cultured rat cortical neurons
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Correction: Contribution of Pannexin1 to Experimental Autoimmune Encephalomyelitis
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AMPA- and P2X7-receptor-mediated facilitation of [3H]d-aspartate release from nerve terminals isolated from the rat caudal brainstem
D’Amico, M., Samengo, I. A., Navarra, P., Taglialatela, M., & Martire, M. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.07.009 · Cited by 14 · see citing works
P2X7 Receptors in Neurohypophysial Terminals: Evidence for their Role in Arginine‐Vasopressin Secretion
Cuadra, A. E., Custer, E. E., Bosworth, E., & Lémos, J. R. (2013) · Journal of Cellular Physiology · doi:10.1002/jcp.24453 · Cited by 10 · see citing works

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The P2X7 Receptor in Inflammatory Diseases: Angel or Demon?
Savio, L. E. B., de Andrade Mello, P., da Silva, C. G., & Coutinho-Silva, R. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00052 · Cited by 437 · see citing works
Purinergic Signalling: Therapeutic Developments
Burnstock, G. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00661 · Cited by 401 · see citing works
Activation of P2X7 receptor and NLRP3 inflammasome assembly in hippocampal glial cells mediates chronic stress-induced depressive-like behaviors
Yue, N., Huang, H., Zhu, X., Han, Q., Wang, Y., Li, B., Liu, Q., Wu, G., Zhang, Y., & Yu, J. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0865-y · Cited by 334 · see citing works
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Burnstock, G. (2018) · Brain and Neuroscience Advances · doi:10.1177/2398212818817494 · Cited by 330 · see citing works
Structural basis for subtype-specific inhibition of the P2X7 receptor
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Microglia in Alzheimer’s disease: pathogenesis, mechanisms, and therapeutic potentials
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Inhibitors of NF-κB and P2X7/NLRP3/Caspase 1 pathway in microglia: Novel therapeutic opportunities in neuroinflammation induced early-stage Alzheimer’s disease
Thawkar, B. S., & Kaur, G. (2018) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2018.11.010 · Cited by 247 · see citing works
The potential of P2X7 receptors as a therapeutic target, including inflammation and tumour progression
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The Dual Role of Microglia in ALS: Mechanisms and Therapeutic Approaches
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Regulation of Microglial Functions by Purinergic Mechanisms in the Healthy and Diseased CNS
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The microglial ATP‐gated ion channel P2X7 as a CNS drug target
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P2X7 Interactions and Signaling – Making Head or Tail of It
Kopp, R., Krautloher, A., Ramírez-Fernández, A., & Nicke, A. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00183 · Cited by 217 · see citing works
Re-evaluation of neuronal P2X7 expression using novel mouse models and a P2X7-specific nanobody
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An introduction to the roles of purinergic signalling in neurodegeneration, neuroprotection and neuroregeneration
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Dorsal horn neurons release extracellular ATP in a VNUT-dependent manner that underlies neuropathic pain
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Microglia control the spread of neurotropic virus infection via P2Y12 signalling and recruit monocytes through P2Y12-independent mechanisms
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Neuronal P2X7 Receptors Revisited: Do They Really Exist?
Illes, P., Khan, T. M., & Rubini, P. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.3103-16.2017 · Cited by 179 · see citing works
P2X7R blockade prevents NLRP3 inflammasome activation and brain injury in a rat model of intracerebral hemorrhage: involvement of peroxynitrite
Feng, L., Chen, Y., Ding, R., Fu, Z., Yang, S., Deng, X., & Zeng, J. (2015) · Journal of Neuroinflammation · doi:10.1186/s12974-015-0409-2 · Cited by 170 · see citing works
Transient P2X7 Receptor Antagonism Produces Lasting Reductions in Spontaneous Seizures and Gliosis in Experimental Temporal Lobe Epilepsy
Jimenez‐Pacheco, A., Dı́az-Hernández, M., Arribas-Blázquez, M., Sanz‐Rodriguez, A., Olivos-Oré, L. A., Artalejo, A. R., Alves, M., Letavic, M. A., Miras‐Portugal, M. T., Conroy, R. M., et al. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.4009-15.2016 · Cited by 161 · see citing works
The NLRP3 inflammasome and COVID-19: Activation, pathogenesis and therapeutic strategies
Zhao, N., Di, B., & Xu, L. (2021) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2021.06.002 · Cited by 156 · see citing works
Pathological α-synuclein exacerbates the progression of Parkinson’s disease through microglial activation
Zhang, Q.-S., Heng, Y., Yuan, Y.-H., & Chen, N.-H. (2017) · Toxicology Letters · doi:10.1016/j.toxlet.2016.11.002 · Cited by 156 · see citing works
The P2X7 Receptor Primes IL-1β and the NLRP3 Inflammasome in Astrocytes Exposed to Mechanical Strain
Albalawi, F., Lu, W., Beckel, J. M., Lim, J. C., McCaughey, S. A., & Mitchell, C. H. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00227 · Cited by 155 · see citing works
Advances in the Potential Biomarkers of Epilepsy
Kobylarek, D., Iwanowski, P. S., Lewandowska, Z., Limphaibool, N., Szafranek, S., Labrzycka, A., & Kozubski, W. P. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00685 · Cited by 153 · see citing works
Role of neuro-immunological factors in the pathophysiology of mood disorders
Bhattacharya, A., Derecki, N. C., Lovenberg, T. W., & Drevets, W. C. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4214-0 · Cited by 149 · see citing works
Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology
Ribeiro, D. E., Oliveira-Giacomelli, Á., Glaser, T., Arnaud-Sampaio, V. F., Andrejew, R., Dieckmann, L., Baranova, J., Lameu, C., Ratajczak, M. Z., & Ulrich, H. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00965-3 · Cited by 145 · see citing works
P2X7 receptor mediates NLRP3 inflammasome activation in depression and diabetes
Wang, D., Wang, H., Gao, H., Zhang, H., Zhang, H., Wang, Q., & Sun, Z. (2020) · Cell & Bioscience · doi:10.1186/s13578-020-00388-1 · Cited by 145 · see citing works
P2X7 Receptors Amplify CNS Damage in Neurodegenerative Diseases
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Microglia and the Purinergic Signaling System
Calovi, S., Mut-Arbona, P., & Sperlágh, B. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.12.021 · Cited by 133 · see citing works
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Inflammasomes as therapeutic targets for A lzheimer's disease
White, C., Lawrence, C. B., Brough, D., & Rivers‐Auty, J. (2016) · Brain Pathology · doi:10.1111/bpa.12478 · Cited by 131 · see citing works
P2X7 Receptor Signaling in Stress and Depression
Ribeiro, D. E., Roncalho, A. L., Glaser, T., Ulrich, H., Wegener, G., & Joca, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20112778 · Cited by 129 · see citing works
The therapeutic potential of purinergic signalling
Burnstock, G. (2017) · Biochemical Pharmacology · doi:10.1016/j.bcp.2017.07.016 · Cited by 127 · see citing works
Principles of inflammasome priming and inhibition: implications for psychiatric disorders
Herman, F. J., & Pasinetti, G. M. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.06.010 · Cited by 115 · see citing works
Recent advances in CNS P2X7 physiology and pharmacology: Focus on neuropsychiatric disorders
Bhattacharya, A. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00030 · Cited by 115 · see citing works
P2X7 Receptor as a Therapeutic Target
Marchi, E. D., Orioli, E., Ben, D. D., & Adinolfi, E. (2016) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2015.11.004 · Cited by 111 · see citing works
Curcumin in Depression: Potential Mechanisms of Action and Current Evidence—A Narrative Review
Ramaholimihaso, T., Bouazzaoui, F., & Kaladjian, A. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.572533 · Cited by 114 · see citing works
Astroglia-Derived ATP Modulates CNS Neuronal Circuits
Illés, P., Burnstock, G., & Tang, Y. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2019.09.006 · Cited by 104 · see citing works
microRNA targeting of the P2X7 purinoceptor opposes a contralateral epileptogenic focus in the hippocampus
Jimenez-Mateos, E. M., Arribas-Blazquez, M., Sanz-Rodriguez, A., Concannon, C., Olivos-Ore, L. A., Reschke, C. R., Mooney, C. M., Mooney, C., Lugara, E., Morgan, J., et al. (2015) · Scientific Reports · doi:10.1038/srep17486 · Cited by 94 · see citing works
Targeting NLRP3 Inflammasome in the Treatment of CNS Diseases
Shao, B., Cao, Q., & Chong, L. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00320 · Cited by 102 · see citing works
Neuroinflammatory In Vitro Cell Culture Models and the Potential Applications for Neurological Disorders
Peng, Y., Chu, S., Yang, Y., Zhang, Z., Pang, Z., & Chen, N. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.671734 · Cited by 102 · see citing works
ATP and adenosine—Two players in the control of seizures and epilepsy development
Beamer, E. H., Kuchukulla, M., Boison, D., & Engel, T. (2021) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2021.102105 · Cited by 99 · see citing works
The ATP-Gated P2X7 Receptor As a Target for the Treatment of Drug-Resistant Epilepsy
Beamer, E. H., Fischer, W., & Engel, T. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00021 · Cited by 100 · see citing works
Electro-Acupuncture Alleviates Chronic Unpredictable Stress-Induced Depressive- and Anxiety-Like Behavior and Hippocampal Neuroinflammation in Rat Model of Depression
Yue, N., Li, B., Yang, L., Han, Q.-Q., Huang, H.-J., Wang, Y.-L., Wang, J., Yu, R., Wu, G.-C., Liu, Q., et al. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00149 · Cited by 100 · see citing works
P2X7 receptor: A potential therapeutic target for autoimmune diseases
Cao, F., Hu, L., Yao, S.-R., Hu, Y., Wang, D., Fan, Y., Pan, G., Tao, S., Zhang, Q., Pan, H., et al. (2019) · Autoimmunity Reviews · doi:10.1016/j.autrev.2019.06.009 · Cited by 98 · see citing works
Imidazopyridine-based selective and multifunctional ligands of biological targets associated with psychiatric and neurodegenerative diseases
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The purinergic P2X7 receptor as a potential drug target to combat neuroinflammation in neurodegenerative diseases
Calzaferri, F., Ruiz‐Ruiz, C., de Diego, A. M. G., de Pascual, R., Méndez‐López, I., Cano‐Abad, M. F., Maneu, V., Rı́os, C. D. L., Gandı́a, L., & de Diego, A. M. G. (2020) · Medicinal Research Reviews · doi:10.1002/med.21710 · Cited by 98 · see citing works
P2X7 Receptor: A Potential Therapeutic Target for Depression?
Deussing, J. M., & Arzt, E. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.07.005 · Cited by 97 · see citing works
Acupuncture-Induced Analgesia
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Glutamate-induced and NMDA receptor-mediated neurodegeneration entails P2Y1 receptor activation
Simões, A. P., Silva, C. G., Marques, J. M., Pochmann, D., Porciúncula, L. O., Ferreira, S., Oses, J. P., Beleza, R. O., Real, J. I., Köfalvi, A., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0351-1 · Cited by 95 · see citing works
18 F-JNJ-64413739, a Novel PET Ligand for the P2X7 Ion Channel: Radiation Dosimetry, Kinetic Modeling, Test-Retest Variability, and Occupancy of the P2X7 Antagonist JNJ-54175446
Koole, M. J. B., Schmidt, M. E., Hijzen, A., Ravenstijn, P. G. M., Vandermeulen, C., Weehaeghe, D. V., Serdons, K., Celen, S., Bormans, G. M., Ceusters, M., et al. (2018) · Journal of Nuclear Medicine · doi:10.2967/jnumed.118.216747 · Cited by 95 · see citing works
ATPergic signalling during seizures and epilepsy
Engel, T., Alves, M., Sheedy, C., & Henshall, D. C. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.11.001 · Cited by 95 · see citing works
Purinergic receptors in psychiatric disorders
Krügel, U. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.10.032 · Cited by 95 · see citing works
Genetically dissecting P2rx7 expression within the central nervous system using conditional humanized mice
Metzger, M. W., Walser, S. M., Aprile-Garcia, F., Dedic, N., Chen, A., Holsboer, F., ARZT, E. S., Wurst, W., & Deussing, J. M. (2016) · Purinergic Signalling · doi:10.1007/s11302-016-9546-z · Cited by 92 · see citing works
Purinergic receptors in embryonic and adult neurogenesis
Oliveira‐Giacomelli, Á., Illés, P., & Ulrich, H. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.10.008 · Cited by 88 · see citing works
ATP-Gated P2X Receptor Channels: Molecular Insights into Functional Roles
Schmid, R., & Evans, R. J. (2018) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020518-114259 · Cited by 86 · see citing works
Connexins and pannexins: At the junction of neuro‐glial homeostasis & disease
Lapato, A. S., & Tiwari-Woodruff, S. K. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.24088 · Cited by 85 · see citing works
P2X7 Receptor Suppression Preserves Blood-Brain Barrier through Inhibiting RhoA Activation after Experimental Intracerebral Hemorrhage in Rats
Zhao, H., Zhang, X., Dai, Z., Feng, Y., Li, Q., Zhang, J. H., Liu, X., Chen, Y., & Feng, H. (2016) · Scientific Reports · doi:10.1038/srep23286 · Cited by 84 · see citing works
A P2X7 receptor antagonist reverses behavioural alterations, microglial activation and neuroendocrine dysregulation in an unpredictable chronic mild stress (UCMS) model of depression in mice
Farooq, R. K., Tanti, A., Ainouche, S., Roger, S., Belzung, C., & Camus, V. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.07.016 · Cited by 83 · see citing works
Inhibiting purinergic P2X7 receptors with the antagonist brilliant blue G is neuroprotective in an intranigral lipopolysaccharide animal model of Parkinson's disease
Wang, X., Xie, X., Luo, X., Shang, H., & He, Z. (2016) · Molecular Medicine Reports · doi:10.3892/mmr.2016.6070 · Cited by 83 · see citing works
Extracellular ATP mediates inflammatory responses in colitis via P2 × 7 receptor signaling
Wan, P., Liu, X., Xiong, Y., Ren, Y., Jiang, C., Lü, N., Guo, Y., & Bai, A. (2016) · Scientific Reports · doi:10.1038/srep19108 · Cited by 83 · see citing works
Mechanism of microglia neuroprotection: Involvement of<scp>P2X</scp>7,<scp>TNF</scp>α, and valproic acid
Masuch, A., Shieh, C., van Rooijen, N., van Calker, D., & Biber, K. (2016) · Glia · doi:10.1002/glia.22904 · Cited by 81 · see citing works
Critical Evaluation of P2X7 Receptor Antagonists in Selected Seizure Models
Fischer, W., Franke, H., Krügel, U., Müller, H., Dinkel, K., Lord, B., Letavic, M. A., Henshall, D. C., & Engel, T. (2016) · PLoS ONE · doi:10.1371/journal.pone.0156468 · Cited by 81 · see citing works
CNS remyelination as a novel reparative approach to neurodegenerative diseases: The roles of purinergic signaling and the P2Y-like receptor GPR17
Fumagalli, M., Lecca, D., & Abbracchio, M. P. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.10.005 · Cited by 81 · see citing works
Serum amyloid A primes microglia for ATP-dependent interleukin-1β release
Facci, L., Barbierato, M., Zusso, M., Skaper, S. D., & Giusti, P. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1205-6 · Cited by 79 · see citing works
Extracellular ATP enhances radiation-induced brain injury through microglial activation and paracrine signaling via P2X7 receptor
Xu, P., Xu, Y., Hu, B., Wang, J., Pan, R., Murugan, M., Wu, L., & Tang, Y. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.06.020 · Cited by 76 · see citing works
AMPK-dependent and independent actions of P2X7 in regulation of mitochondrial and lysosomal functions in microglia
Sekar, P., Huang, D.-Y., Hsieh, S.-L. E., Chang, S., & Lin, W. (2018) · Cell Communication and Signaling · doi:10.1186/s12964-018-0293-3 · Cited by 80 · see citing works
Regulation of P2X7 receptor expression and function in the brain
Jimenez-Mateos, E. M., Smith, J., Nicke, A., & Engel, T. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2018.12.008 · Cited by 79 · see citing works
Pathological ATPergic Signaling in Major Depression and Bipolar Disorder
Illés, P., Verkhratsky, A., & Tang, Y. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00331 · Cited by 77 · see citing works
Synthesis of [11C]GSK1482160 as a new PET agent for targeting P2X7 receptor
Gao, M., Wang, M., Green, M. A., Hutchins, G. D., & Zheng, Q. (2015) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2015.03.021 · Cited by 77 · see citing works
Cellular mechanisms of peroxynitrite-induced neuronal death
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Authors: Sperlágh, B., & Illes, P.
Affiliations: HUN-REN Institute of Experimental Medicine (HU)
Corresponding author: Sperlágh, Beáta
ORCID: Sperlágh, Beáta
Venue: Trends in Pharmacological Sciences
Publisher: Elsevier BV
Published: 2014-10
Volume: 35
Issue: 10
Pages: 537-547
ISSN: 0165-6147 (ISSN-L)
DOI: 10.1016/j.tips.2014.08.002
OpenAlex: W2133942268
Cited by: 390
References: 164
Citations by year: 2026: 21 · 2025: 20 · 2024: 35 · 2023: 25 · 2022: 32 · 2021: 30 · 2020: 37 · 2019: 35 · 2018: 43 · 2017: 44 · 2016: 38 · 2015: 27 · 2014: 3
FWCI: 4.52
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in Pharmacological Sciences (publishedVersion)
PubMed (publishedVersion)
Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords: P2X7 receptor, ATP, central nervous system disorders, inflammasome, neuroinflammation, stroke, neurotrauma, epilepsy, neuropathic pain, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, mood disorders, therapeutic target
MeSH terms: Animals, Mental Disorders, Humans, Neurodegenerative Diseases, Receptors, Purinergic P2X7, Purinergic P2X Receptor Antagonists

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P2X7 receptor: an emerging target in central nervous system diseases

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