Inflammasome Elements in Epilepsy and Seizures Publisher



Saleki K^{1, 2, 3} ; Mohamadi M⁴ ; Alijanizadeh P^{1, 2} ; Rezaei N^{5, 6, 7}
Source: Translational Neuroimmunology: Neuroinflammation: Volume 7 Published:2023

Abstract

The inflammasomes refer to cytosolic multimolecular complexes within the innate immunity which drive inflammatory feedbacks. Based on structure, inflammasomes are divided into subclasses, such as NLRPs, NLRCs, and AIMs. These inflammasome components function as pattern recognition receptors (PRRs). That is, they can sense pathogen-associated molecular patterns (PAMPs), danger-associated molecular patterns (DAMPs), or homeostasis-altering molecular processes (HAMPs). Then, functional inflammasomes undergo assembly. The contribution of inflammasomes to neuroinflammation has been largely explored in the central nervous system (CNS). Neuroinflammation contributes to the pathogenesis and progression of many neuropsychiatric diseases, such as epilepsy. After CNS injury, inflammasome induction results in the release of neuroinflammatory components, such as interleukin (IL)-1β, IL-18, and high-mobility group box-1 (HMGB1), thereby resulting in epileptogenesis. Following inflammasome induction, nerve cells and glia release HMGB1 that is a ubiquitous nuclear protein as well as a target and biological marker for epilepsy; moreover, preclinical and clinical research on epilepsy therapeutics has focused on targeting inflammasomes such as NLRP1 and NLRP3. In addition to such direct evidence, inflammasomes can indirectly contribute to epileptogenesis; for instance, risk factors for epilepsy, including atherosclerosis, diabetes, hypertension, obesity, and infection are associated with the induction of inflammasomes, including NLRP3, NLRP1, NLRC4, and AIM2. In the present chapter, we discuss introductory information regarding inflammasomes, function of inflammasomes in the immunopathology and treatment of epilepsy, and insight into future translational research on epilepsy. © 2023 Elsevier Inc. All rights reserved.