P2X purinoceptor 7 (P2X7) (P2X7R)

The P2X purinoceptor 7 (P2X7R) is a trimeric ligand-gated ion channel that is uniquely activated by high concentrations of extracellular adenosine triphosphate (ATP), which typically signals cellular distress or damage [1]. Unlike other members of the P2X family, prolonged activation of P2X7R leads to the formation of a large, non-selective pore that allows the passage of molecules up to 900 Daltons, eventually triggering cell death via apoptosis or necrosis [2]. It is highly expressed on cells of the innate immune system, particularly macrophages, monocytes, and microglia, where it serves as a critical trigger for the NLRP3 inflammasome [3]. This activation results in the maturation and secretion of potent pro-inflammatory cytokines, most notably interleukin-1 beta (IL-1β) and interleukin-18 [4]. Because of its central role in orchestrating inflammatory responses, P2X7R has become a major therapeutic target for treating chronic inflammatory diseases, neuropathic pain, and neurodegenerative conditions like Alzheimer's disease [5]. Pharmaceutical development has largely focused on small-molecule antagonists designed to cross the blood-brain barrier for CNS indications or act systemically for autoimmune disorders [6]. [1] UniProt Consortium, P2RX7 - P2X purinoceptor 7 - Homo sapiens, UniProt ID P54132. [2] Di Virgilio, F., et al. (2017), The P2X7 Receptor: A Main Player in Inflammation, Immunity, 47(1), 15-31. [3] Burnstock, G., & Knight, G. E. (2018), The potential of P2X7 receptors as a therapeutic target, Purinergic Signalling, 14(2), 113-132. [4] Bhattacharya, A., & Biber, K. (2016), The role of P2X7 receptors in CNS function and disease, Current Opinion in Pharmacology, 26, 33-39. [5] Savio, L. E., et al. (2018), P2X7 receptor as a therapeutic target in inflammation and cancer, Expert Opinion on Therapeutic Targets, 22(3), 219-231. [6] ClinicalTrials.gov, A Study of JNJ-54175446 in Participants With Major Depressive Disorder, Identifier: NCT02508272.

Other names

P2RX7Purinergic receptor P2X7P2Z receptorATP receptorP2X7 receptor

Antagonism of the P2X7 receptor to inhibit ATP-induced cation influx, macropore formation, and NLRP3 inflammasome-mediated release of pro-inflammatory cytokines.