Inflammasomes in CNS Diseases.

Abstract

Neuroinflammation is a common pathological feature in almostall neurological diseases and is a response triggered as a consequence of the chronic activation of the innate immune response in the CNS against a variety of stimuli, including infection, traumatic brain injury, toxic metabolites, aggregated proteins, or autoimmunity. Crucial mediators of this neurinflammatoryprocess are theintracellular protein complexes known as inflammasomes which can be triggered by pathogens as well as pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). However, chronic inflammasome activation can eventually result in cellular death and tissue damage, leading to the release of DAMPs that can reactivate the inflammasome, thereby propagating a vicious cycle of inflammation. The primary cells involved in CNS inflammasome activation are the immunocompetent microglia and the infiltratingmacrophages into the CNS. However,astrocytes and neurons alsoexpress inflammasomes, and the understanding of how they are engaged in the pathogenesis of a variety of neurological diseases is crucial to develop effective therapeutic approaches for CNS pathologies that are propagated by chronicinflammasome activation. This chapter covers the activation mechanisms of relevant inflammasomes in the brain and summarizes their roles in the pathogenesis and progression of different neurological conditions.