Role of inflammasomes and neuroinflammation in epilepsy

Immunol Rev. 2025 Jan;329(1):e13421. doi: 10.1111/imr.13421. Epub 2024 Nov 10.

Abstract

Epilepsy is a brain disorder characterized by recurrent seizures, which are brief episodes of abnormal electrical activity in the brain and involuntary movement that can lead to physical injury and loss of consciousness. Seizures are canonically accompanied by increased inflammatory cytokine production that promotes neuroinflammation, brain pathology, and seizure propagation. Understanding the source of pro-inflammatory cytokines which promote seizure pathogenesis could be a gateway to precision epilepsy drug design. This review discusses the inflammasome in epilepsy including its role in seizure propagation and negative impacts on brain health. The inflammasome is a multiprotein complex that coordinates IL-1β and IL-18 production in response to tissue damage, cellular stress, and infection. Clinical evidence for inflammasome signaling in epileptogenesis is reviewed followed by a discussion of emerging strategies to modulate inflammasome activity in epilepsy.

Keywords: Gasdermin D; IL‐1 family cytokines; IL‐18; IL‐1β; NOD‐like receptor; epilepsy; inflammasomes; neuroinflammation; seizure.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / immunology
  • Brain / metabolism
  • Brain / pathology
  • Cytokines / metabolism
  • Epilepsy* / etiology
  • Epilepsy* / immunology
  • Epilepsy* / metabolism
  • Humans
  • Inflammasomes* / metabolism
  • Interleukin-1beta / metabolism
  • Neuroinflammatory Diseases* / etiology
  • Neuroinflammatory Diseases* / immunology
  • Neuroinflammatory Diseases* / metabolism
  • Signal Transduction

Substances

  • Inflammasomes
  • Interleukin-1beta
  • Cytokines