The potential of P2X7 receptors as a therapeutic target, including inflammation and tumour progression
Geoffrey Burnstock1,2,3, Gillian E Knight4
1Autonomic Neuroscience Centre, University College Medical School, Rowland Hill Street, London, NW3 2PF, UK. g.burnstock@ucl.ac.uk.
Abstract:
Seven P2X ion channel nucleotide receptor subtypes have been cloned and characterised. P2X7 receptors (P2X7R) are unusual in that there are extra amino acids in the intracellular C terminus. Low concentrations of ATP open cation channels sometimes leading to cell proliferation, whereas high concentrations of ATP open large pores that release inflammatory cytokines and can lead to apoptotic cell death. Since many diseases involve inflammation and immune responses, and the P2X7R regulates inflammation, there has been recent interest in the pathophysiological roles of P2X7R and the potential of P2X7R antagonists to treat a variety of diseases. These include neurodegenerative diseases, psychiatric disorders, epilepsy and a number of diseases of peripheral organs, including the cardiovascular, airways, kidney, liver, bladder, skin and musculoskeletal. The potential of P2X7R drugs to treat tumour progression is discussed.
Insights
The P2X7 receptor (P2X7R) plays a key role in inflammation and cell death. Targeting P2X7R with drugs may offer new treatments for inflammatory diseases, neurodegenerative conditions, and cancer.
Area of Science:
- Ion channel research
- Immunology
- Pharmacology
Background:
- Seven P2X ion channel nucleotide receptor subtypes are known.
- P2X7 receptors (P2X7R) possess unique intracellular C-terminal amino acid extensions.
- P2X7R activation by ATP can lead to cation channel opening or large pore formation.
Purpose of the Study:
- To explore the pathophysiological roles of P2X7R.
- To investigate the therapeutic potential of P2X7R antagonists.
- To discuss P2X7R drug applications in various diseases and tumor progression.
Main Methods:
- Characterization of P2X7 receptor function.
- Analysis of ATP concentration-dependent effects on P2X7R.
- Review of existing literature on P2X7R in disease.
Main Results:
- Low ATP concentrations activate cation channels, potentially inducing cell proliferation.
- High ATP concentrations induce large pores, releasing inflammatory cytokines and causing cell death.
- P2X7R is implicated in inflammatory and immune responses.
Conclusions:
- P2X7R is a significant regulator of inflammation.
- P2X7R antagonists show promise for treating inflammatory diseases.
- Therapeutic strategies targeting P2X7R may be beneficial for neurodegenerative disorders, psychiatric conditions, and cancer.
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