Role of Innate Immune Receptor TLR4 and its endogenous ligands in epileptogenesis

Paudel YN 1 , Angelopoulou E 2 , Akyuz E 3 , Piperi C 4 , Othman I 5 , Shaikh MF 6

Affiliations 

  • 1 Neuropharmacology Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia. Electronic address: yam.paudel@monash.edu
  • 2 Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: angelthal@med.uoa.gr
  • 3 Yozgat Bozok University, Faculty of Medicine, Department of Biophysics, 66100 Yozgat, Turkey. Electronic address: enes.akyuz@yobu.edu.tr
  • 4 Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: cpiperi@med.uoa.gr
  • 5 Neuropharmacology Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia. Electronic address: Iekhsan.othman@monash.edu
  • 6 Neuropharmacology Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia. Electronic address: Farooq.shaikh@monash.edu
Pharmacol Res, 2020 10;160:105172.
PMID: 32871246 DOI: 10.1016/j.phrs.2020.105172

Abstract

Understanding the interplay between the innate immune system, neuroinflammation, and epilepsy might offer a novel perspective in the quest of exploring new treatment strategies. Due to the complex pathology underlying epileptogenesis, no disease-modifying treatment is currently available that might prevent epilepsy after a plausible epileptogenic insult despite the advances in pre-clinical and clinical research. Neuroinflammation underlies the etiopathogenesis of epilepsy and convulsive disorders with Toll-like receptor (TLR) signal transduction being highly involved. Among TLR family members, TLR4 is an innate immune system receptor and lipopolysaccharide (LPS) sensor that has been reported to contribute to epileptogenesis by regulating neuronal excitability. Herein, we discuss available evidence on the role of TLR4 and its endogenous ligands, the high mobility group box 1 (HMGB1) protein, the heat shock proteins (HSPs) and the myeloid related protein 8 (MRP8), in epileptogenesis and post-traumatic epilepsy (PTE). Moreover, we provide an account of the promising findings of TLR4 modulation/inhibition in experimental animal models with therapeutic impact on seizures.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

MeSH terms
Similar publications