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Purinergic Signaling in Neuroinflammation 2.0
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Purinergic Signaling in Neuroinflammation 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (15 November 2022) | Viewed by 7447

Special Issue Editors

Prof. Dr. Peter Illes

E-Mail Website
Guest Editor
Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, Universitaet Leipzig, Leipzig, Germany
Interests: neuropharmacology; neurotoxicology; purinergic mechanisms; modulation of synaptic transmission; glial cells; necrosis/apoptosis; analgesia; learning and memory; epileptic state
Special Issues, Collections and Topics in MDPI journals
Dr. Dmitry Aminin

E-Mail Website
Guest Editor
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 690022 Vladivostok, Russia
Interests: biochemistry; cell biology; structure and function of biological membranes; mechanism of biological activity of natural and synthetic biologically active substances; new drug discovery; molecular targets; toxicology; ecotoxicology; biomarkers; biosensors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is clear today that the physiological effect of extracellular ATP is mediated by its interaction with specific purinergic receptors. All purinergic receptors are divided into P1-purinoreceptors (the main ligand is adenosine) and P2-purinoreceptors (the main ligands are ATP/ADP and UTP/UDP). Each of the subtypes is divided into a number of families. For instance, P2 receptors are divided into P2X and P2Y receptors according to the mechanism by which their effect is realized: P2Ys are G-protein coupled receptors, while P2X receptors are ligand-operated ion channels (or ionotropic receptors). P2X receptors are important molecular therapeutic targets, and their malfunctioning results in serious complications in the physiology of humans and animals and can cause dangerous diseases. The search for compounds that can modulate the function of purinergic receptors can result in the creation of new drugs that are effective in the treatment of diseases of the central and peripheral nervous system and immune system, including neuroinflammation, hypoxia/ischemia, epilepsy and neuropathic pain. In this Special Issue, we wish to offer a platform for high-quality publications on the latest advances on the identification of P2X/Y and P1 (A1, A2A, A2B and A3) receptor blockers, their functions and their regulation; the characterization of these receptor signaling networks and crosstalk; mechanisms underlying the role of purinoceptors in neurodegenerative illnesses as well as chronic neuronal changes following acute noxious damage; and therapeutic opportunities associated with the regulation of purinergic receptor activity. This Special Issue will be of interest to researchers working on cell signaling, neurology and immunology and also to chemical biologists interested in drug discovery, as well as clinicians.

Prof. Dr. Peter Illes
Dr. Dmitry Aminin
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • purinergic receptors
  • P2X, P2Y and P1 family receptors
  • signaling mechanisms
  • neuroinflammation
  • neurodegeneration and neuroregeneration
  • epilepsy
  • hypoxia/ischemia
  • neuropathic and inflammatory pain
  • receptor antagonists
  • enzyme inhibitors
  • drug discovery

Related Special Issue

Published Papers (3 papers)

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Research

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19 pages, 4212 KiB  
Article
Nucleotide-Induced Nanoscale Changes in the Mechanical Properties of Rat Cerebellar Astrocytes: Selective Stimulation and Blocking of the Purinergic Receptor P2X7
by Juan Carlos Gil-Redondo, Jagoba Iturri, Yaiza Trueba, María Benito-León, Raquel Pérez-Sen, Esmerilda G. Delicado, José Luis Toca-Herrera and Felipe Ortega
Int. J. Mol. Sci. 2022, 23(19), 11927; https://doi.org/10.3390/ijms231911927 - 07 Oct 2022
Cited by 2 | Viewed by 1361
Abstract
As members of the family of nucleotide receptors, P2X7 receptors are of particular interest due to their unique structural and pharmacological characteristics. As ATP-gated ionic channels, P2X7 receptors in their activation elicit membrane depolarization; extracellular calcium influx; and activation of several downstream intracellular [...] Read more.
As members of the family of nucleotide receptors, P2X7 receptors are of particular interest due to their unique structural and pharmacological characteristics. As ATP-gated ionic channels, P2X7 receptors in their activation elicit membrane depolarization; extracellular calcium influx; and activation of several downstream intracellular signaling pathways, some of them independent of the ionic channel activity. Further interactions of P2X7 receptors and cytoskeleton-related proteins have also been confirmed, and we previously described the effects of P2X7 receptor stimulation on the morphology of rat cerebellar astrocytes. In the present work, we used time-lapse video microscopy and atomic force microscopy (AFM) to elucidate the effects of P2X7 receptor stimulation on the morphology, migratory capabilities, and mechanical properties of rat cerebellar astrocytes in vitro. Stimulation of P2X7 receptors with the selective agonist BzATP specifically caused an increase in cell size, motility, and number of membrane protrusions of the astrocytes in culture. These effects were reverted when cells were previously treated with the competitive antagonist of P2X7R, A 438079. AFM analysis also showed an increase in cell stiffness and viscosity after P2X7 receptor stimulation. Surprisingly, these effects on the mechanical properties of the cell were not blocked by the treatment with the antagonist. Fluorescence microscopy analysis of the actin cytoskeleton showed an increase in actin stress fibers after BzATP treatment, an effect that again was not blocked by previous treatment with the antagonist, further confirming that the effects of P2X7 receptors on the cytoskeleton of astrocytes are, at least in part, independent of the ionic channel activity. Full article
(This article belongs to the Special Issue Purinergic Signaling in Neuroinflammation 2.0)
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Review

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14 pages, 1395 KiB  
Review
A2B Adenosine Receptor in Idiopathic Pulmonary Fibrosis: Pursuing Proper Pit Stop to Interfere with Disease Progression
by Wiwin Is Effendi and Tatsuya Nagano
Int. J. Mol. Sci. 2023, 24(5), 4428; https://doi.org/10.3390/ijms24054428 - 23 Feb 2023
Cited by 3 | Viewed by 1951
Abstract
Purine nucleotides and nucleosides are involved in various human physiological and pathological mechanisms. The pathological deregulation of purinergic signaling contributes to various chronic respiratory diseases. Among the adenosine receptors, A2B has the lowest affinity such that it was long considered to have little [...] Read more.
Purine nucleotides and nucleosides are involved in various human physiological and pathological mechanisms. The pathological deregulation of purinergic signaling contributes to various chronic respiratory diseases. Among the adenosine receptors, A2B has the lowest affinity such that it was long considered to have little pathophysiological significance. Many studies suggest that A2BAR plays protective roles during the early stage of acute inflammation. However, increased adenosine levels during chronic epithelial injury and inflammation might activate A2BAR, resulting in cellular effects relevant to the progression of pulmonary fibrosis. Full article
(This article belongs to the Special Issue Purinergic Signaling in Neuroinflammation 2.0)
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24 pages, 1582 KiB  
Review
Beyond Seizure Control: Treating Comorbidities in Epilepsy via Targeting of the P2X7 Receptor
by Beatriz Gil, Jonathon Smith, Yong Tang, Peter Illes and Tobias Engel
Int. J. Mol. Sci. 2022, 23(4), 2380; https://doi.org/10.3390/ijms23042380 - 21 Feb 2022
Cited by 11 | Viewed by 3474
Abstract
Epilepsy is one of the most common chronic diseases of the central nervous system (CNS). Treatment of epilepsy remains, however, a clinical challenge with over 30% of patients not responding to current pharmacological interventions. Complicating management of treatment, epilepsy comes with multiple comorbidities, [...] Read more.
Epilepsy is one of the most common chronic diseases of the central nervous system (CNS). Treatment of epilepsy remains, however, a clinical challenge with over 30% of patients not responding to current pharmacological interventions. Complicating management of treatment, epilepsy comes with multiple comorbidities, thereby further reducing the quality of life of patients. Increasing evidence suggests purinergic signalling via extracellularly released ATP as shared pathological mechanisms across numerous brain diseases. Once released, ATP activates specific purinergic receptors, including the ionotropic P2X7 receptor (P2X7R). Among brain diseases, the P2X7R has attracted particular attention as a therapeutic target. The P2X7R is an important driver of inflammation, and its activation requires high levels of extracellular ATP to be reached under pathological conditions. Suggesting the therapeutic potential of drugs targeting the P2X7R for epilepsy, P2X7R expression increases following status epilepticus and during epilepsy, and P2X7R antagonism modulates seizure severity and epilepsy development. P2X7R antagonism has, however, also been shown to be effective in treating conditions most commonly associated with epilepsy such as psychiatric disorders and cognitive deficits, which suggests that P2X7R antagonisms may provide benefits beyond seizure control. This review summarizes the evidence suggesting drugs targeting the P2X7R as a novel treatment strategy for epilepsy with a particular focus of its potential impact on epilepsy-associated comorbidities. Full article
(This article belongs to the Special Issue Purinergic Signaling in Neuroinflammation 2.0)
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