High mobility group box 1 (HMGB1) as a novel frontier in epileptogenesis

from pathogenesis to therapeutic approaches

Yam Nath Paudel, Bridgette D. Semple, Nigel C. Jones, Iekhsan Othman, Mohd Farooq Shaikh

Research output: Contribution to journalReview ArticleResearchpeer-review

Abstract

Epilepsy is a serious neurological condition exhibiting complex pathology and deserving of more serious attention. More than 30% of people with epilepsy are not responsive to more than 20 anti-epileptic drugs currently available, reflecting an unmet clinical need for novel therapeutic strategies. Not much is known about the pathogenesis of epilepsy, but evidence indicates that neuroinflammation might contribute to the onset and progression of epilepsy following acquired brain insults. However, the molecular mechanisms underlying these pathophysiological processes are yet to be fully understood. The emerging research suggests that high-mobility group box protein 1 (HMGB1), a DNA-binding protein that is both actively secreted by inflammatory cells and released by necrotic cells, might contribute to the pathogenesis of epilepsy. HMGB1 as an initiator and amplifier of neuroinflammation, and its activation is implicated in the propagation of seizures in animal models. The current review will highlight the potential role of HMGB1 in the pathogenesis of epilepsy, and implications of HMGB1-targeted therapies against epilepsy. HMGB1 in this context is an emerging concept deserving further exploration. Increased understanding of HMGB1 in seizures and epilepsy will pave the way in designing novel and innovative therapeutic strategies that could modify the disease course or prevent its development. (Figure presented.).

Original languageEnglish
Number of pages16
JournalJournal of Neurochemistry
DOIs
Publication statusAccepted/In press - 15 Jan 2019

Keywords

  • epilepsy
  • HMGB1
  • HMGB1 inhibitors
  • inflammation
  • RAGE
  • TLR4

Cite this

@article{cb0e3956db6e40fb8b7fd817ae3538af,
title = "High mobility group box 1 (HMGB1) as a novel frontier in epileptogenesis: from pathogenesis to therapeutic approaches",
abstract = "Epilepsy is a serious neurological condition exhibiting complex pathology and deserving of more serious attention. More than 30{\%} of people with epilepsy are not responsive to more than 20 anti-epileptic drugs currently available, reflecting an unmet clinical need for novel therapeutic strategies. Not much is known about the pathogenesis of epilepsy, but evidence indicates that neuroinflammation might contribute to the onset and progression of epilepsy following acquired brain insults. However, the molecular mechanisms underlying these pathophysiological processes are yet to be fully understood. The emerging research suggests that high-mobility group box protein 1 (HMGB1), a DNA-binding protein that is both actively secreted by inflammatory cells and released by necrotic cells, might contribute to the pathogenesis of epilepsy. HMGB1 as an initiator and amplifier of neuroinflammation, and its activation is implicated in the propagation of seizures in animal models. The current review will highlight the potential role of HMGB1 in the pathogenesis of epilepsy, and implications of HMGB1-targeted therapies against epilepsy. HMGB1 in this context is an emerging concept deserving further exploration. Increased understanding of HMGB1 in seizures and epilepsy will pave the way in designing novel and innovative therapeutic strategies that could modify the disease course or prevent its development. (Figure presented.).",
keywords = "epilepsy, HMGB1, HMGB1 inhibitors, inflammation, RAGE, TLR4",
author = "Paudel, {Yam Nath} and Semple, {Bridgette D.} and Jones, {Nigel C.} and Iekhsan Othman and Shaikh, {Mohd Farooq}",
year = "2019",
month = "1",
day = "15",
doi = "10.1111/jnc.14663",
language = "English",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",

}

High mobility group box 1 (HMGB1) as a novel frontier in epileptogenesis : from pathogenesis to therapeutic approaches. / Paudel, Yam Nath; Semple, Bridgette D.; Jones, Nigel C.; Othman, Iekhsan; Shaikh, Mohd Farooq.

In: Journal of Neurochemistry, 15.01.2019.

Research output: Contribution to journalReview ArticleResearchpeer-review

TY - JOUR

T1 - High mobility group box 1 (HMGB1) as a novel frontier in epileptogenesis

T2 - from pathogenesis to therapeutic approaches

AU - Paudel, Yam Nath

AU - Semple, Bridgette D.

AU - Jones, Nigel C.

AU - Othman, Iekhsan

AU - Shaikh, Mohd Farooq

PY - 2019/1/15

Y1 - 2019/1/15

N2 - Epilepsy is a serious neurological condition exhibiting complex pathology and deserving of more serious attention. More than 30% of people with epilepsy are not responsive to more than 20 anti-epileptic drugs currently available, reflecting an unmet clinical need for novel therapeutic strategies. Not much is known about the pathogenesis of epilepsy, but evidence indicates that neuroinflammation might contribute to the onset and progression of epilepsy following acquired brain insults. However, the molecular mechanisms underlying these pathophysiological processes are yet to be fully understood. The emerging research suggests that high-mobility group box protein 1 (HMGB1), a DNA-binding protein that is both actively secreted by inflammatory cells and released by necrotic cells, might contribute to the pathogenesis of epilepsy. HMGB1 as an initiator and amplifier of neuroinflammation, and its activation is implicated in the propagation of seizures in animal models. The current review will highlight the potential role of HMGB1 in the pathogenesis of epilepsy, and implications of HMGB1-targeted therapies against epilepsy. HMGB1 in this context is an emerging concept deserving further exploration. Increased understanding of HMGB1 in seizures and epilepsy will pave the way in designing novel and innovative therapeutic strategies that could modify the disease course or prevent its development. (Figure presented.).

AB - Epilepsy is a serious neurological condition exhibiting complex pathology and deserving of more serious attention. More than 30% of people with epilepsy are not responsive to more than 20 anti-epileptic drugs currently available, reflecting an unmet clinical need for novel therapeutic strategies. Not much is known about the pathogenesis of epilepsy, but evidence indicates that neuroinflammation might contribute to the onset and progression of epilepsy following acquired brain insults. However, the molecular mechanisms underlying these pathophysiological processes are yet to be fully understood. The emerging research suggests that high-mobility group box protein 1 (HMGB1), a DNA-binding protein that is both actively secreted by inflammatory cells and released by necrotic cells, might contribute to the pathogenesis of epilepsy. HMGB1 as an initiator and amplifier of neuroinflammation, and its activation is implicated in the propagation of seizures in animal models. The current review will highlight the potential role of HMGB1 in the pathogenesis of epilepsy, and implications of HMGB1-targeted therapies against epilepsy. HMGB1 in this context is an emerging concept deserving further exploration. Increased understanding of HMGB1 in seizures and epilepsy will pave the way in designing novel and innovative therapeutic strategies that could modify the disease course or prevent its development. (Figure presented.).

KW - epilepsy

KW - HMGB1

KW - HMGB1 inhibitors

KW - inflammation

KW - RAGE

KW - TLR4

UR - http://www.scopus.com/inward/record.url?scp=85061498989&partnerID=8YFLogxK

U2 - 10.1111/jnc.14663

DO - 10.1111/jnc.14663

M3 - Review Article

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

ER -