Submitted Successfully!
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Ver. Summary Created by Modification Content Size Created at Operation
1 -- 1823 2023-07-11 12:06:45 |
2 update layout Meta information modification 1823 2023-07-12 03:40:03 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Cevoli, F.; Arnould, B.; Peralta, F.A.; Grutter, T. Macropore Formation and Current Facilitation in P2X7. Encyclopedia. Available online: (accessed on 06 December 2023).
Cevoli F, Arnould B, Peralta FA, Grutter T. Macropore Formation and Current Facilitation in P2X7. Encyclopedia. Available at: Accessed December 06, 2023.
Cevoli, Federico, Benoit Arnould, Francisco Andrés Peralta, Thomas Grutter. "Macropore Formation and Current Facilitation in P2X7" Encyclopedia, (accessed December 06, 2023).
Cevoli, F., Arnould, B., Peralta, F.A., & Grutter, T.(2023, July 11). Macropore Formation and Current Facilitation in P2X7. In Encyclopedia.
Cevoli, Federico, et al. "Macropore Formation and Current Facilitation in P2X7." Encyclopedia. Web. 11 July, 2023.
Macropore Formation and Current Facilitation in P2X7

Macropore formation and current facilitation are intriguing phenomena associated with ATP-gated P2X7 receptors (P2X7). Macropores are large pores formed in the cell membrane that allow the passage of large molecules. The precise mechanisms underlying macropore formation remain poorly understood, but recent evidence suggests two alternative pathways: a direct entry through the P2X7 pore itself, and an indirect pathway triggered by P2X7 activation involving additional proteins, such as TMEM16F channel/scramblase. On the other hand, current facilitation refers to the progressive increase in current amplitude and activation kinetics observed with prolonged or repetitive exposure to ATP. Various mechanisms, including the activation of chloride channels and intrinsic properties of P2X7, have been proposed to explain this phenomenon.

P2X7 current facilitation macropore formation

1. Introduction

P2X7 receptors (P2X7) are part of the purinergic family, which consists of ATP-gated P2X receptors (P2X). In mammals, this family comprises seven subunits, namely P2X1 to P2X7, which assemble in the membrane to form homo- or heterotrimeric channels [1][2][3][4][5]. Among P2X receptors, P2X7 demonstrates a unique low sensitivity to ATP. It requires unusually high millimolar-range concentrations of ATP to become activated. As these elevated concentrations are typically found at sites of cell injury, P2X7 is therefore referred to as a “danger-sensing receptor” [6]. Consequently, P2X7 is widely expressed in immune cells, including macrophages and microglia, which are capable of detecting the abnormal release of extracellular ATP (eATP).
It has long been shown that eATP can act as a signaling molecule [7]. Despite having a short half-life of a few seconds at therapeutic concentrations (0.1 mM in human airways) [8], it is often associated with relatively long-lasting events, particularly those related to inflammatory or pro-inflammatory cellular states [9]. Consequently, P2X7 is involved in several physiological and pathological processes, including inflammation, immune responses, cell proliferation and programmed cell death, such as apoptosis and pyroptosis. In the nervous system, for example, P2X7 has been shown to play a crucial role in various neuropathological conditions, including neurodegeneration, chronic pain and brain injury [10]. The accumulation of eATP at inflammatory sites triggers a range of pathophysiological responses via P2X7, with the most notable being the activation of the NOD-, LPR- and pyrin domain-containing protein 3 (NLRP3) inflammasome in the cytoplasm of mononuclear and polymorphonuclear phagocytes [6]. In the context of neuroinflammation, P2X7-driven inflammasome activation in microglia initiates a cascade of events leading to the production and release of several pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β) as well as reactive oxygen species (ROS) [11]. Furthermore, P2X7 has been implicated in the pathogenesis of chronic pain states [12], where its activation triggers the development and maintenance of conditions such as neuropathic pain, inflammatory pain and cancer pain [13][14]. Due to its ability to induce the release of pro-inflammatory cytokines that may eventually lead to cell death, P2X7 is considered a promising drug target for numerous pathophysiological conditions, particularly in the field of neuroimmunology [15][16][17][18][19][20][21].
When eATP binds to P2X7, it triggers the rapid opening of the transmembrane channel, enabling the passage of small monovalent ions, such as sodium (Na+) and potassium (K+), as well as divalent cations such as calcium (Ca2+), across the cell membrane. Unlike other P2X receptors, P2X7 typically does not undergo channel desensitization, which is a temporary inactivation that terminates ion flux despite ATP remaining bound to the receptor. Instead, P2X7 undergoes a facilitation process where currents progressively increase with repetitive or prolonged agonist application [1][22]. Stimulation of P2X7 also leads to the formation of a phenomenon known as P2X7 macropore formation, which involves the permeabilization of the cell membrane to high molecular weight species [22][23]. While other P2X receptors also exhibit permeability to organic cations [24][25][26], the distinct feature of P2X7 macropore formation lies in its ability to allow the passage of nanometer-scale molecules [27]. Macropore formation has also been implicated in cell death mechanisms and certain pathological states, including chronic pain [12]. Despite several hypotheses proposed to explain macropore formation and current facilitation [23][24][25][28], the underlying mechanisms remain poorly understood.

2. P2X7 Structures

Although the first atomic resolution structure of P2X receptors was published in 2009 [29], the pioneering structures of P2X7 were not released until 2016. These structures were resolved using X-ray crystallography and were based on the receptor obtained from the giant panda [30]. These structures confirmed the trimeric architecture of the ion channel and exhibited an overall structural similarity to previously crystallized P2X receptors [29][30][31][32], with each subunit resembling the characteristic dolphin-like shape. They also confirmed the presence of three ATP-binding sites at the subunit boundaries in the extracellular domain and the presence of two transmembrane segments (TM1 and TM2 from each subunit) that form the ion-conducting pore. However, these structures were highly truncated in both the N- and C-termini due to the requirement of the crystallization process. Since the intracellularly located C-terminus is significant for P2X7, these initial structures provided limited information about its cytoplasmic domain. Notably, P2X7 possesses a unique and unusually large C-terminus that is not present in other determined or predicted P2X structures [33]. Importantly, this C-terminus plays a crucial role in initiating apoptosis [22][34][35][36][37][38][39]. Consequently, in 2019, Mansoor’s group successfully determined the full-length structure of rat P2X7 [40] using single-particle cryo-electron microscopy (cryo-EM). This groundbreaking accomplishment provided invaluable insights into the structural characteristics of P2X7 and significantly advanced our understanding of this receptor. The full-length structure was solved in both the absence (apo state) and the presence of ATP (ATP-bound state), revealing novel structural elements in the cytoplasmic domain (Figure 1A). In comparison to other P2X receptors [4], the cytoplasmic domain of P2X7 significantly protrudes into the cytosol and features two unexpected components: the “C-cys anchor” and the “ballast” (Figure 1B). The C-cys anchor is a cysteine-rich loop consisting of 18 amino acid residues [40][41]. It serves as a connection between TM2 and the cytoplasmic cap, a highly intertwined element found in P2X3 receptors, which is thought to play a role in channel desensitization [32]. The C-cys anchor contains several palmitoylated residues, and it has been demonstrated that it prevents channel desensitization by physically anchoring the palmitoylated groups to the membrane, thus restricting the movement of the cytoplasmic cap [40]. The second element is the ballast, located beneath the cytoplasmic cap and C-cys anchor, which folds into an autonomous domain without any structural homologue in the Protein Data Bank. Surprisingly, three GDP-binding sites and three dinuclear Zn2+-binding sites have been discovered within the ballast. However, the role of the ballast, GDP and Zn2+ remains completely unknown. Notably, the presence of an intracellularly located GDP-binding site gives the P2X7 the appearance of having two nucleotide-binding sites emerging from the membrane—one on the extracellular side and the other on the intracellular side (Figure 1A).
Figure 1. (A). Cryo-EM structure of rat P2X7 (pdb code: 6u9w) embedded in a lipid bilayer, represented as spheres. The two nucleotide-binding sites, ATP and GDP, are indicated. (B). Ribbon representation of the same view, highlighting relevant structural features (ATP and GDP in green, Zn2+ in violet, palmitoyl groups in orange and F11 residue in red). Dotted lines depict the approximate position of the membrane boundaries.

3. The Role of Macropore Formation and Current Facilitation in the P2X7-Associated Diseases

A relevant question is whether macropore formation and current facilitation contribute to P2X7-related diseases. While the precise extent of their contribution is not yet fully understood, existing evidence strongly supports that specific alterations in these features, particularly macropore formation, have functional implications.
Over the past two decades, it has become evident that P2X7 plays a significant role in highly prevalent diseases. In the central nervous system, P2X7 has been implicated in neurodegenerative diseases [42][43], psychiatric disorders [44], neuropathic pain [45], epilepsy [43][46] and multiple sclerosis [43][47]. P2X7 has been shown to be upregulated in microglia surrounding the accumulation of amyloid beta (Aβ) peptides [48], a hallmark of Alzheimer’s disease (AD). In murine models, inhibiting or lacking P2X7 has been associated with a decrease in amyloid plaques and Aβ load [49][50][51]. Furthermore, the P2X7-dependent exacerbation of Huntington’s disease symptoms has been observed in murine models, and treatment with brilliant blue G, a P2X7 antagonist, leads to a reduction in the overall pattern of neurodegeneration. These findings suggest a generalized role of this receptor in neurodegenerative diseases [52]. However, the contribution of macropore formation and current facilitation to the progression of AD is not yet clear, and further studies are necessary.
Regarding neuropathic pain, there is strong evidence supporting the contribution of macropore formation. Studies have shown that the naturally occurring P451L allelic mutation, located in the ballast (unfortunately not resolved in the single-particle cryo-EM structures), reduces sensitivity to ATP-induced macropore formation while not affecting channel function [53]. Haplotype mapping in mice has demonstrated that this mutation alleviates the effects of mechanical allodynia, suggesting that specifically targeting macropore formation while preserving cation channel activity could be a novel therapeutic strategy for reducing pain in individuals carrying P2RX7 haplotypes that confer a high risk for chronic pain [12]. Numerous polymorphisms have now been described, some resulting in loss of function and others leading to gain of function [14].
In cancer, P2X7 has also been found to be involved in tumor progression [54][55]. Studies have provided insights into the relationship between the ion channel and the macropore features of P2X7 in vivo. The tumor microenvironment can contain sufficient levels of eATP for prolonged P2X7 activation [56], and it is suggested that these levels peak in localized microdomains near the plasma membrane [57]. Interestingly, it has been found that high levels of ATP in the tumor microenvironment might promote the expression of non-pore functional P2X7 (nfP2X7) or the truncated isoform P2X7B in tumor cells [58][59]. These P2X7 variants are fully uncoupled from macropore formation and lack cytotoxic activity but are still associated with a cytoplasmic increase in Ca2+, supporting proliferation. Moreover, the wild-type P2X7 is incapable of rescuing cells from death caused by knockdown of endogenous nfP2X7 [58]. This suggests the involvement of an intricate cancer cell survival mechanism that encompasses the ion channel function of P2X7 along with the inhibition of macropore activity. Additionally, these forms of P2X7 have been found to be overexpressed in tissue samples taken from patients compared to the control group [58].
In summary, the exact implications of the macropore formation in pathology are not yet fully understood; however, the available evidence strongly supports its significant involvement. To unravel the complexities of this intricate phenomenon, it is crucial to develop innovative approaches that enable the construction of a robust and comprehensive model incorporating molecular, cellular, and in vivo investigations. Disentangling the specific characteristics of individual P2X7 functions poses a tremendous challenge. Of particular significance is the Herculean task of deciphering P2X7-dependent macropore formation in pathological diseases, as isolating this feature from the ion channel activity proves exceptionally difficult, particularly in more complex models such as living animals.


  1. North, R.A. Molecular physiology of P2X receptors. Physiol. Rev. 2002, 82, 1013–1067.
  2. Coddou, C.; Yan, Z.; Obsil, T.; Huidobro-Toro, J.P.; Stojilkovic, S.S. Activation and regulation of purinergic P2X receptor channels. Pharmacol. Rev. 2011, 63, 641–683.
  3. Sheng, D.; Hattori, M. Recent progress in the structural biology of P2X receptors. Proteins 2022, 90, 1779–1785.
  4. Illes, P.; Muller, C.E.; Jacobson, K.A.; Grutter, T.; Nicke, A.; Fountain, S.J.; Kennedy, C.; Schmalzing, G.; Jarvis, M.F.; Stojilkovic, S.S.; et al. Update of P2X receptor properties and their pharmacology: IUPHAR Review 30. Br. J. Pharmacol. 2021, 178, 489–514.
  5. Habermacher, C.; Dunning, K.; Chataigneau, T.; Grutter, T. Molecular structure and function of P2X receptors. Neuropharmacology 2016, 104, 18–30.
  6. Di Virgilio, F.; Dal Ben, D.; Sarti, A.C.; Giuliani, A.L.; Falzoni, S. The P2X7 Receptor in Infection and Inflammation. Immunity 2017, 47, 15–31.
  7. Burnstock, G. Purinergic nerves. Pharmacol. Rev. 1972, 24, 509–581.
  8. Picher, M.; Burch, L.H.; Boucher, R.C. Metabolism of P2 receptor agonists in human airways: Implications for mucociliary clearance and cystic fibrosis. J. Biol. Chem. 2004, 279, 20234–20241.
  9. Di Virgilio, F.; Vultaggio-Poma, V.; Falzoni, S.; Giuliani, A.L. Extracellular ATP: A powerful inflammatory mediator in the central nervous system. Neuropharmacology 2023, 224, 109333.
  10. Ren, W.J.; Illes, P. Involvement of P2X7 receptors in chronic pain disorders. Purinergic Signal. 2022, 18, 83–92.
  11. Illes, P. P2X7 Receptors Amplify CNS Damage in Neurodegenerative Diseases. Int. J. Mol. Sci. 2020, 21, 5996.
  12. Sorge, R.E.; Trang, T.; Dorfman, R.; Smith, S.B.; Beggs, S.; Ritchie, J.; Austin, J.S.; Zaykin, D.V.; Vander Meulen, H.; Costigan, M.; et al. Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity. Nat. Med. 2012, 18, 595–599.
  13. Hu, S.Q.; Hu, J.L.; Zou, F.L.; Liu, J.P.; Luo, H.L.; Hu, D.X.; Wu, L.D.; Zhang, W.J. P2X7 receptor in inflammation and pain. Brain Res. Bull. 2022, 187, 199–209.
  14. Lara, R.; Adinolfi, E.; Harwood, C.A.; Philpott, M.; Barden, J.A.; Di Virgilio, F.; McNulty, S. P2X7 in Cancer: From Molecular Mechanisms to Therapeutics. Front. Pharmacol. 2020, 11, 793.
  15. Calzaferri, F.; Ruiz-Ruiz, C.; de Diego, A.M.G.; de Pascual, R.; Mendez-Lopez, I.; Cano-Abad, M.F.; Maneu, V.; de Los Rios, C.; Gandia, L.; Garcia, A.G. The purinergic P2X7 receptor as a potential drug target to combat neuroinflammation in neurodegenerative diseases. Med. Res. Rev. 2020, 40, 2427–2465.
  16. Bhattacharya, A.; Ceusters, M. Targeting neuroinflammation with brain penetrant P2X7 antagonists as novel therapeutics for neuropsychiatric disorders. Neuropsychopharmacology 2020, 45, 234–235.
  17. Bhattacharya, A.; Lord, B.; Grigoleit, J.S.; He, Y.; Fraser, I.; Campbell, S.N.; Taylor, N.; Aluisio, L.; O’Connor, J.C.; Papp, M.; et al. Neuropsychopharmacology of JNJ-55308942: Evaluation of a clinical candidate targeting P2X7 ion channels in animal models of neuroinflammation and anhedonia. Neuropsychopharmacology 2018, 43, 2586–2596.
  18. Lord, B.; Aluisio, L.; Shoblock, J.R.; Neff, R.A.; Varlinskaya, E.I.; Ceusters, M.; Lovenberg, T.W.; Carruthers, N.; Bonaventure, P.; Letavic, M.A.; et al. Pharmacology of a novel central nervous system-penetrant P2X7 antagonist JNJ-42253432. J. Pharmacol. Exp. Ther. 2014, 351, 628–641.
  19. Bhattacharya, A.; Wang, Q.; Ao, H.; Shoblock, J.R.; Lord, B.; Aluisio, L.; Fraser, I.; Nepomuceno, D.; Neff, R.A.; Welty, N.; et al. Pharmacological characterization of a novel centrally permeable P2X7 receptor antagonist: JNJ-47965567. Br. J. Pharmacol. 2013, 170, 624–640.
  20. Lord, B.; Ameriks, M.K.; Wang, Q.; Fourgeaud, L.; Vliegen, M.; Verluyten, W.; Haspeslagh, P.; Carruthers, N.I.; Lovenberg, T.W.; Bonaventure, P.; et al. A novel radioligand for the ATP-gated ion channel P2X7: JNJ-54232334. Eur. J. Pharmacol. 2015, 765, 551–559.
  21. Savio, L.E.B.; de Andrade Mello, P.; da Silva, C.G.; Coutinho-Silva, R. The P2X7 Receptor in Inflammatory Diseases: Angel or Demon? Front. Pharmacol. 2018, 9, 52.
  22. Surprenant, A.; Rassendren, F.; Kawashima, E.; North, R.A.; Buell, G. The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). Science 1996, 272, 735–738.
  23. Di Virgilio, F.; Schmalzing, G.; Markwardt, F. The Elusive P2X7 Macropore. Trends Cell. Biol. 2018, 28, 392–404.
  24. Virginio, C.; MacKenzie, A.; Rassendren, F.A.; North, R.A.; Surprenant, A. Pore dilation of neuronal P2X receptor channels. Nat. Neurosci. 1999, 2, 315–321.
  25. Khakh, B.S.; Bao, X.R.; Labarca, C.; Lester, H.A. Neuronal P2X transmitter-gated cation channels change their ion selectivity in seconds. Nat. Neurosci. 1999, 2, 322–330.
  26. Harkat, M.; Peverini, L.; Cerdan, A.H.; Dunning, K.; Beudez, J.; Martz, A.; Calimet, N.; Specht, A.; Cecchini, M.; Chataigneau, T.; et al. On the permeation of large organic cations through the pore of ATP-gated P2X receptors. Proc. Natl. Acad. Sci. USA 2017, 114, E3786–E3795.
  27. Browne, L.E.; Compan, V.; Bragg, L.; North, R.A. P2X7 receptor channels allow direct permeation of nanometer-sized dyes. J. Neurosci. 2013, 33, 3557–3566.
  28. Peverini, L.; Beudez, J.; Dunning, K.; Chataigneau, T.; Grutter, T. New Insights Into Permeation of Large Cations through ATP-Gated P2X Receptors. Front. Mol. Neurosci. 2018, 11, 265.
  29. Kawate, T.; Michel, J.C.; Birdsong, W.T.; Gouaux, E. Crystal structure of the ATP-gated P2X(4) ion channel in the closed state. Nature 2009, 460, 592–598.
  30. Karasawa, A.; Kawate, T. Structural basis for subtype-specific inhibition of the P2X7 receptor. Elife 2016, 5, e22153.
  31. Hattori, M.; Gouaux, E. Molecular mechanism of ATP binding and ion channel activation in P2X receptors. Nature 2012, 485, 207–212.
  32. Mansoor, S.E.; Lu, W.; Oosterheert, W.; Shekhar, M.; Tajkhorshid, E.; Gouaux, E. X-ray structures define human P2X(3) receptor gating cycle and antagonist action. Nature 2016, 538, 66–71.
  33. Bennetts, F.M.; Mobbs, J.I.; Ventura, S.; Thal, D.M. The P2X1 receptor as a therapeutic target. Purinergic Signal. 2022, 18, 421–433.
  34. Costa-Junior, H.M.; Sarmento Vieira, F.; Coutinho-Silva, R. C terminus of the P2X7 receptor: Treasure hunting. Purinergic Signal. 2011, 7, 7–19.
  35. el-Moatassim, C.; Dubyak, G.R. A novel pathway for the activation of phospholipase D by P2z purinergic receptors in BAC1.2F5 macrophages. J. Biol. Chem. 1992, 267, 23664–23673.
  36. Humphreys, B.D.; Dubyak, G.R. Induction of the P2z/P2X7 nucleotide receptor and associated phospholipase D activity by lipopolysaccharide and IFN-gamma in the human THP-1 monocytic cell line. J. Immunol. 1996, 157, 5627–5637.
  37. Wilson, H.L.; Wilson, S.A.; Surprenant, A.; North, R.A. Epithelial membrane proteins induce membrane blebbing and interact with the P2X7 receptor C terminus. J. Biol. Chem. 2002, 277, 34017–34023.
  38. Cheewatrakoolpong, B.; Gilchrest, H.; Anthes, J.C.; Greenfeder, S. Identification and characterization of splice variants of the human P2X7 ATP channel. Biochem. Biophys. Res. Commun. 2005, 332, 17–27.
  39. Adinolfi, E.; Cirillo, M.; Woltersdorf, R.; Falzoni, S.; Chiozzi, P.; Pellegatti, P.; Callegari, M.G.; Sandona, D.; Markwardt, F.; Schmalzing, G.; et al. Trophic activity of a naturally occurring truncated isoform of the P2X7 receptor. FASEB J. 2010, 24, 3393–3404.
  40. McCarthy, A.E.; Yoshioka, C.; Mansoor, S.E. Full-Length P2X(7) Structures Reveal How Palmitoylation Prevents Channel Desensitization. Cell 2019, 179, 659–670.e13.
  41. Jiang, L.H.; Rassendren, F.; Mackenzie, A.; Zhang, Y.H.; Surprenant, A.; North, R.A. N-methyl-D-glucamine and propidium dyes utilize different permeation pathways at rat P2X(7) receptors. Am. J. Physiol. Cell. Physiol. 2005, 289, C1295–C1302.
  42. Le Feuvre, R.; Brough, D.; Rothwell, N. Extracellular ATP and P2X7 receptors in neurodegeneration. Eur. J. Pharmacol. 2002, 447, 261–269.
  43. Kanellopoulos, J.M.; Delarasse, C. Pleiotropic Roles of P2X7 in the Central Nervous System. Front. Cell. Neurosci. 2019, 13, 401.
  44. Lucae, S.; Salyakina, D.; Barden, N.; Harvey, M.; Gagne, B.; Labbe, M.; Binder, E.B.; Uhr, M.; Paez-Pereda, M.; Sillaber, I.; et al. P2RX7, a gene coding for a purinergic ligand-gated ion channel, is associated with major depressive disorder. Hum. Mol. Genet. 2006, 15, 2438–2445.
  45. Chessell, I.P.; Hatcher, J.P.; Bountra, C.; Michel, A.D.; Hughes, J.P.; Green, P.; Egerton, J.; Murfin, M.; Richardson, J.; Peck, W.L.; et al. Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain. Pain 2005, 114, 386–396.
  46. Beamer, E.; Fischer, W.; Engel, T. The ATP-Gated P2X7 Receptor As a Target for the Treatment of Drug-Resistant Epilepsy. Front. Neurosci. 2017, 11, 21.
  47. Amadio, S.; Parisi, C.; Piras, E.; Fabbrizio, P.; Apolloni, S.; Montilli, C.; Luchetti, S.; Ruggieri, S.; Gasperini, C.; Laghi-Pasini, F.; et al. Modulation of P2X7 Receptor during Inflammation in Multiple Sclerosis. Front. Immunol. 2017, 8, 1529.
  48. McLarnon, J.G.; Ryu, J.K.; Walker, D.G.; Choi, H.B. Upregulated expression of purinergic P2X(7) receptor in Alzheimer disease and amyloid-beta peptide-treated microglia and in peptide-injected rat hippocampus. J. Neuropathol. Exp. Neurol. 2006, 65, 1090–1097.
  49. Diaz-Hernandez, J.I.; Gomez-Villafuertes, R.; Leon-Otegui, M.; Hontecillas-Prieto, L.; Del Puerto, A.; Trejo, J.L.; Lucas, J.J.; Garrido, J.J.; Gualix, J.; Miras-Portugal, M.T.; et al. In vivo P2X7 inhibition reduces amyloid plaques in Alzheimer’s disease through GSK3beta and secretases. Neurobiol. Aging 2012, 33, 1816–1828.
  50. Chen, X.; Hu, J.; Jiang, L.; Xu, S.; Zheng, B.; Wang, C.; Zhang, J.; Wei, X.; Chang, L.; Wang, Q. Brilliant Blue G improves cognition in an animal model of Alzheimer’s disease and inhibits amyloid-beta-induced loss of filopodia and dendrite spines in hippocampal neurons. Neuroscience 2014, 279, 94–101.
  51. Martin, E.; Amar, M.; Dalle, C.; Youssef, I.; Boucher, C.; Le Duigou, C.; Bruckner, M.; Prigent, A.; Sazdovitch, V.; Halle, A.; et al. New role of P2X7 receptor in an Alzheimer’s disease mouse model. Mol. Psychiatry 2019, 24, 108–125.
  52. Diaz-Hernandez, M.; Diez-Zaera, M.; Sanchez-Nogueiro, J.; Gomez-Villafuertes, R.; Canals, J.M.; Alberch, J.; Miras-Portugal, M.T.; Lucas, J.J. Altered P2X7-receptor level and function in mouse models of Huntington’s disease and therapeutic efficacy of antagonist administration. FASEB J. 2009, 23, 1893–1906.
  53. Adriouch, S.; Dox, C.; Welge, V.; Seman, M.; Koch-Nolte, F.; Haag, F. Cutting edge: A natural P451L mutation in the cytoplasmic domain impairs the function of the mouse P2X7 receptor. J. Immunol. 2002, 169, 4108–4112.
  54. Adinolfi, E.; De Marchi, E.; Orioli, E.; Pegoraro, A.; Di Virgilio, F. Role of the P2X7 receptor in tumor-associated inflammation. Curr. Opin. Pharmacol. 2019, 47, 59–64.
  55. Janho Dit Hreich, S.; Benzaquen, J.; Hofman, P.; Vouret-Craviari, V. To inhibit or to boost the ATP/P2RX7 pathway to fight cancer-that is the question. Purinergic Signal. 2021, 17, 619–631.
  56. Pellegatti, P.; Raffaghello, L.; Bianchi, G.; Piccardi, F.; Pistoia, V.; Di Virgilio, F. Increased level of extracellular ATP at tumor sites: In vivo imaging with plasma membrane luciferase. PLoS ONE 2008, 3, e2599.
  57. Di Virgilio, F. Purines, purinergic receptors, and cancer. Cancer Res. 2012, 72, 5441–5447.
  58. Gilbert, S.M.; Oliphant, C.J.; Hassan, S.; Peille, A.L.; Bronsert, P.; Falzoni, S.; Di Virgilio, F.; McNulty, S.; Lara, R. ATP in the tumour microenvironment drives expression of nfP2X(7), a key mediator of cancer cell survival. Oncogene 2019, 38, 194–208.
  59. Giuliani, A.L.; Colognesi, D.; Ricco, T.; Roncato, C.; Capece, M.; Amoroso, F.; Wang, Q.G.; De Marchi, E.; Gartland, A.; Di Virgilio, F.; et al. Trophic activity of human P2X7 receptor isoforms A and B in osteosarcoma. PLoS ONE 2014, 9, e107224.
Subjects: Others
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to : , , ,
View Times: 87
Revisions: 2 times (View History)
Update Date: 12 Jul 2023