PMID- 36438559 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221129 IS - 2296-634X (Print) IS - 2296-634X (Electronic) IS - 2296-634X (Linking) VI - 10 DP - 2022 TI - Pannexin1 channels-a potential therapeutic target in inflammation. PG - 1020826 LID - 10.3389/fcell.2022.1020826 [doi] LID - 1020826 AB - An exaggerated inflammatory response is the hallmark of a plethora of disorders. ATP is a central signaling molecule that orchestrates the initiation and resolution of the inflammatory response by enhancing activation of the inflammasome, leukocyte recruitment and activation of T cells. ATP can be released from cells through pannexin (Panx) channels, a family of glycoproteins consisting of three members, Panx1, Panx2, and Panx3. Panx1 is ubiquitously expressed and forms heptameric channels in the plasma membrane mediating paracrine and autocrine signaling. Besides their involvement in the inflammatory response, Panx1 channels have been shown to contribute to different modes of cell death (i.e., pyroptosis, necrosis and apoptosis). Both genetic ablation and pharmacological inhibition of Panx1 channels decrease inflammation in vivo and contribute to a better outcome in several animal models of inflammatory disease involving various organs, including the brain, lung, kidney and heart. Up to date, several molecules have been identified to inhibit Panx1 channels, for instance probenecid (Pbn), mefloquine (Mfq), flufenamic acid (FFA), carbenoxolone (Cbx) or mimetic peptides like (10)Panx1. Unfortunately, the vast majority of these compounds lack specificity and/or serum stability, which limits their application. The recent availability of detailed structural information on the Panx1 channel from cryo-electron microscopy studies may open up innovative approaches to acquire new classes of synthetic Panx1 channel blockers with high target specificity. Selective inhibition of Panx1 channels may not only limit acute inflammatory responses but may also prove useful in chronic inflammatory diseases, thereby improving human health. Here, we reviewed the current knowledge on the role of Panx1 in the initiation and resolution of the inflammatory response, we summarized the effects of Panx1 inhibition in inflammatory pathologies and recapitulate current Panx1 channel pharmacology with an outlook towards future approaches. CI - Copyright (c) 2022 Rusiecka, Tournier, Molica and Kwak. FAU - Rusiecka, Olga M AU - Rusiecka OM AD - Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland. AD - Geneva Centre for Inflammation Research, Faculty of Medicine, University of Geneva, Geneva, Switzerland. FAU - Tournier, Malaury AU - Tournier M AD - Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland. AD - Geneva Centre for Inflammation Research, Faculty of Medicine, University of Geneva, Geneva, Switzerland. FAU - Molica, Filippo AU - Molica F AD - Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland. AD - Geneva Centre for Inflammation Research, Faculty of Medicine, University of Geneva, Geneva, Switzerland. FAU - Kwak, Brenda R AU - Kwak BR AD - Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland. AD - Geneva Centre for Inflammation Research, Faculty of Medicine, University of Geneva, Geneva, Switzerland. LA - eng PT - Journal Article PT - Review DEP - 20221109 PL - Switzerland TA - Front Cell Dev Biol JT - Frontiers in cell and developmental biology JID - 101630250 PMC - PMC9682086 OTO - NOTNLM OT - Panx1 OT - cell death OT - channels OT - inflammatory response OT - signaling OT - therapeutics COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/11/29 06:00 MHDA- 2022/11/29 06:01 PMCR- 2022/01/01 CRDT- 2022/11/28 04:19 PHST- 2022/08/16 00:00 [received] PHST- 2022/10/20 00:00 [accepted] PHST- 2022/11/28 04:19 [entrez] PHST- 2022/11/29 06:00 [pubmed] PHST- 2022/11/29 06:01 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 1020826 [pii] AID - 10.3389/fcell.2022.1020826 [doi] PST - epublish SO - Front Cell Dev Biol. 2022 Nov 9;10:1020826. doi: 10.3389/fcell.2022.1020826. eCollection 2022.