title: The microglial ATP-gated ion channel P2X7 as a CNS drug target.
abstract: Based on promising preclinical evidence, microglial P2X7 has increasingly being recognized as a target for therapeutic intervention in neurological and psychiatric diseases. However, despite this knowledge no P2X7-related drug has yet entered clinical trials with respect to CNS diseases. We here discuss the current literature on P2X7 being a drug target and identify unsolved issues and still open questions that have hampered the development of P2X7 dependent therapeutic approaches for CNS diseases. It is concluded here that the lack of brain penetrating P2X7 antagonists is a major obstacle in the field and that central P2X7 is a yet untested clinical drug target. In the CNS, microglial P2X7 activation causes neuroinflammation, which in turn plays a role in various CNS disorders. This has resulted in a surge of brain penetrant P2X7 antagonists. P2X7 is a viable, clinically untested CNS drug target. GLIA 2016;64:1772-1787.
authors.affiliation: LLC. Neuroscience Drug Discovery, Janssen Research & Development, 3210 Merryfield Row, San Diego, California.
authors.forename: Anindya
authors.initials: A
authors.lastname: Bhattacharya
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Freiburg, Hauptstrasse 5, Freiburg, Germany.|Department of Neuroscience, University Medical Center Groningen, University of Groningen, Ant. Deusinglaan 1, AV Groningen, The Netherlands.
authors.forename: Knut
authors.initials: K
authors.lastname: Biber
mesh_terms: D000818:Animals; D002493:Central Nervous System Diseases / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D058905:Purinergic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*
chemical_list: D058905:Purinergic Agents; D058486:Receptors, Purinergic P2X7
keywords: IL-1β; P2X7; depression; microglia; mood disorders; neurodegeneration; neuroinflammation; pain