TY - JOUR
T1 - Role of innate immune receptor TLR4 and its endogenous ligands in epileptogenesis
AU - Paudel, Yam Nath
AU - Angelopoulou, Efthalia
AU - Akyuz, Enes
AU - Piperi, Christina
AU - Othman, Iekhsan
AU - Shaikh, Mohd. Farooq
PY - 2020/10
Y1 - 2020/10
N2 - 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.
AB - 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.
KW - Epileptogenesis
KW - HMGB1
KW - Innate immunity
KW - Neuroinflammation
KW - Post-traumatic epilepsy
KW - TLR4
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=woscharlessturt_pure&SrcAuth=WosAPI&KeyUT=WOS:000598123900013&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1016/j.phrs.2020.105172
DO - 10.1016/j.phrs.2020.105172
M3 - Review article
C2 - 32871246
SN - 1043-6618
VL - 160
JO - Pharmacological Research
JF - Pharmacological Research
M1 - 105172
ER -