Referenced in: none

Automatically associated channels: Kv6.1 , SK1

Title: The neuroprotective effect of a specific P2X₇ receptor antagonist derives from its ability to inhibit assembly of the NLRP3 inflammasome in glial cells.

Authors: Niamh Murphy, Thelma R Cowley, Jill C Richardson, David Virley, Neil Upton, Daryl Walter, Marina A Lynch

Journal, date & volume: Brain Pathol., 2012 May , 22, 295-306

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21933296

Abstract
Release of interleukin (IL)-1β from immunocompetent cells requires formation of the NACHT, LLR and PYD domains-containing protein 3 (NLRP3) inflammasome and caspase 1 activation. Adenosine 5'-triphosphate (ATP), acting on the P2X(7) receptor, is one factor that stimulates inflammasome assembly. We show that a novel specific P2X(7) receptor antagonist, GSK1370319A, inhibits ATP-induced increase in IL-1β release and caspase 1 activation in lipopolysaccharide (LPS)-primed mixed glia by blocking assembly of the inflammasome in a pannexin 1-dependent manner. GSK1370319A also inhibits ATP-induced subregion-specific neuronal loss in hippocampal organotypic slice cultures, which is dependent on its ability to prevent inflammasome assembly in glia. Significantly, GSK1370319A attenuates age-related deficits in long-term potentiation (LTP) and inhibits the accompanying age-related caspase 1 activity. We conclude that inhibiting P2X(7) receptor-activated NLRP3 inflammasome formation and the consequent IL-1β release from glia preserve neuronal viability and synaptic activity.