Inflammasomes in neurological diseases: emerging pathogenic and therapeutic concepts

Abstract

Inflammasome activation in the central nervous system occurs in both health and disease. Inflammasomes are cytosolic protein complexes that sense specific infectious or host stimuli and initiate inflammatory responses through caspase activation. Assembly of inflammasomes results in caspase-1-mediated proteolytic cleavage and release of the pro-inflammatory cytokines, interleukin-1β and interleukin-18, with initiation of pyroptosis, an inflammatory programmed cell death. Recent developments in the inflammasome field have uncovered novel molecular mechanisms that contribute to a broad range of neurological disorders including those associated with specific mutations in inflammasome genes as well as diseases modulated by inflammasome activation. This update focuses on recent developments in the field of inflammasome biology highlighting different inflammasome activators and pathways discovered in the nervous system. We also discuss targeted therapies that regulate inflammasomes and improve neurological outcomes.

Keywords: ASC; caspase-1; inflammasome; interleukin-1beta; pyroptosis.