Targeting Inflammasomes to Treat Neurological Diseases

Inflammasomes are multimeric protein complexes that can sense a plethora of microbe- and damage-associated molecular signals. They play important roles in innate immunity and are key regulators of inflammation in health and disease. Inflammasome-mediated processing and secretion of pro-inflammatory cytokines such as interleukin 1β (IL-1β) and IL-18 and induction of pyroptosis, a pro-inflammatory form of cell death, has been associated with the development and progression of common immune-mediated and degenerative central nervous system (CNS) diseases such as Alzheimer's disease, multiple sclerosis, brain injury, stroke, epilepsy, Parkinson's disease, and amyotrophic lateral sclerosis. A growing number of pharmacological compounds inhibiting inflammasome activation and signalling shows therapeutic efficacy in preclinical models of the aforementioned disease conditions. Here, we illustrate regulatory mechanisms of inflammasome activation during CNS homeostasis and tissue injury. We highlight the evidence for inflammasome activation as a mechanistic underpinning in a wide range of CNS diseases and critically discuss the promise and potential limitations therapeutic strategies that aim to inhibit the inflammasome components in neurological disorders. This article is protected by copyright. All rights reserved.