Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.
Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW 2522, Australia.
Int J Mol Sci. 2022 May 20;23(10):5739. doi: 10.3390/ijms23105739.
The adenosine 5'-triphosphate-gated P2X4 receptor channel is a promising target in neuroinflammatory disorders, but the ability to effectively target these receptors in models of neuroinflammation has presented a constant challenge. As such, the exact role of P2X4 receptors and their cell signalling mechanisms in human physiology and pathophysiology still requires further elucidation. To this end, research into the molecular mechanisms of P2X4 receptor activation, modulation, and inhibition has continued to gain momentum in an attempt to further describe the role of P2X4 receptors in neuroinflammation and other disease settings. Here we provide an overview of the current understanding of the P2X4 receptor, including its expression and function in cells involved in neuroinflammatory signalling. We discuss the pharmacology of P2X4 receptors and provide an overview of P2X4-targeting molecules, including agonists, positive allosteric modulators, and antagonists. Finally, we discuss the use of P2X4 receptor modulators and antagonists in models of neuroinflammatory cell signalling and disease.
三磷酸腺苷门控 P2X4 受体通道是神经炎症性疾病的一个很有前途的靶点，但在神经炎症模型中有效地靶向这些受体一直是一个挑战。因此，P2X4 受体及其细胞信号机制在人体生理学和病理生理学中的确切作用仍需要进一步阐明。为此，对 P2X4 受体激活、调节和抑制的分子机制的研究继续保持强劲势头，试图进一步描述 P2X4 受体在神经炎症和其他疾病环境中的作用。在这里，我们概述了对 P2X4 受体的现有认识，包括其在涉及神经炎症信号的细胞中的表达和功能。我们讨论了 P2X4 受体的药理学，并概述了 P2X4 靶向分子，包括激动剂、正变构调节剂和拮抗剂。最后，我们讨论了 P2X4 受体调节剂和拮抗剂在神经炎症细胞信号和疾病模型中的应用。
