Role of innate immune receptor TLR4 and its endogenous ligands in epileptogenesis

Yam Nath Paudel, Efthalia Angelopoulou, Enes Akyuz, Christina Piperi, Iekhsan Othman, Mohd Farooq Shaikh

Research output: Contribution to journalReview ArticleOtherpeer-review

28 Citations (Scopus)

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.

Original languageEnglish
Article number105172
Number of pages13
JournalPharmacological Research
Volume160
DOIs
Publication statusPublished - Oct 2020

Keywords

  • Epileptogenesis
  • HMGB1
  • Innate immunity
  • Neuroinflammation
  • Post-traumatic epilepsy
  • TLR4

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