The P2X4 receptor (P2X4) is an ATP-gated cation channel that is highly permeable to Ca and widely expressed in neuronal and glial cell types throughout the central nervous system (CNS). A growing body of evidence indicates that P2X4 plays key roles in numerous central disorders. P2X4 trafficking is highly regulated and consequently in normal situations, P2X4 is present on the plasma membrane at low density and found mostly within intracellular endosomal/lysosomal compartments. An increase in the de novo expression and/or surface density of P2X4 has been observed in microglia and/or neurons during pathological states. This review aims to summarize knowledge on P2X4 functions in CNS disorders and provide some insights into the relative contributions of neuronal and glial P2X4 in pathological contexts. However, determination of the cell-specific functions of P2X4 along with its intracellular and cell surface roles remain to be elucidated before its potential as a therapeutic target in multiple disorders can be defined.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674530 | PMC |
| http://dx.doi.org/10.1007/s12264-020-00570-y | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Repeated administration of a subanesthetic dose of ketamine results in impaired motor and cognitive behavior and differential expression of hippocampal P2X1 and P2X7 receptors in adult mice.
Behav Brain Res
January 2025
Laboratorio de Neurobiología, División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica (IPICYT), San Luis Potosí, Mexico. Electronic address:
Ketamine hydrochloride serves multiple purposes, including its use as a general anesthetic, treatment for depression, and recreational drug. In studies involving rodents, ketamine is utilized as a model for schizophrenia. However, it is unclear whether age affects the behavioral response induced by repeated ketamine administration and if it modifies the expression levels of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and purinergic receptors (P2X1, P2X4, P2X7).
View Article and Find Full Text PDFHuman P2X4 receptor gating is modulated by a stable cytoplasmic cap and a unique allosteric pocket.
Sci Adv
January 2025
Department of Chemical Physiology & Biochemistry, Oregon Health & Science University, Portland, OR 97239, USA.
P2X receptors (P2XRs) are adenosine 5'-triphosphate (ATP)-gated ion channels comprising homomeric and heteromeric trimers of seven subtypes (P2X1-P2X7) that confer different rates of desensitization. The helical recoil model of P2XR desensitization proposes stability of the cytoplasmic cap sets the rate of desensitization, but timing of its formation is unclear for slow-desensitizing P2XRs. We report cryo-electron microscopy structures of full-length wild-type human P2X4 receptor in apo closed, antagonist-bound inhibited, and ATP-bound desensitized states.
View Article and Find Full Text PDFLipopolysaccharide-Neutralizing Peptide Modulates P2X7 Receptor-Mediated Interleukin-1β Release.
ACS Pharmacol Transl Sci
January 2025
Pharmaceutical Institute, Pharmacology and Toxicology, University of Bonn, Gerhard-Domagk-Str. 3, 53121 Bonn, Germany.
Lipopolysaccharide (LPS)-neutralizing peptides are emerging as new potential therapeutic modalities to treat sepsis and skin infections. Purinergic ligand-gated ion channels (P2X receptors) play a critical role in various biological processes, including inflammation. Recent drug development efforts have significantly focused on the modulation of P2X receptors.
View Article and Find Full Text PDFNaphtho[1,2-][1,4]diazepinedione-Based P2X4 Receptor Antagonists from Structure-Activity Relationship Studies toward PET Tracer Development.
J Med Chem
January 2025
European Institute for Molecular Imaging (EIMI), University of Muenster, Roentgenstr. 16, 48149 Muenster, Germany.
The P2X4 receptor is implicated in various pathological conditions, including neuropathic pain and cancer. This study reports the development of 1,4-naphthodiazepinedione-based P2X4 receptor antagonists aimed at both therapeutic applications and potential use as PET tracers for imaging P2X4 receptor expression in cancer. Structure-activity relationship studies aided by docking studies and molecular dynamics simulations led to a series of compounds with potent P2X4 receptor antagonism, promising inhibition of interleukin-1β release in THP-1 cells and suitability for radiolabeling with fluorine-18.
View Article and Find Full Text PDFCholesterol metabolites modulate ionotropic P2X4 and P2X7 receptor current in microglia cells.
Neuropharmacology
March 2025
Dept. of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, Catania, Italy. Electronic address:
The central nervous system is a well-known steroidogenic tissue producing, among others, cholesterol metabolites such as neuroactive steroids, oxysterols and steroid hormones. It is well known that these endogenous molecules affect several receptor classes, including ionotropic GABAergic and NMDA glutamatergic receptors in neurons. It has been shown that also ionotropic purinergic (P2X) receptors are cholesterol metabolites' targets.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!