Molecular isoforms of high-mobility group box 1 are mechanistic biomarkers for epilepsy

The Journal of Clinical Investigation
Lauren Elizabeth WalkerMunir Pirmohamed

Abstract

Approximately 30% of epilepsy patients do not respond to antiepileptic drugs, representing an unmet medical need. There is evidence that neuroinflammation plays a pathogenic role in drug-resistant epilepsy. The high-mobility group box 1 (HMGB1)/TLR4 axis is a key initiator of neuroinflammation following epileptogenic injuries, and its activation contributes to seizure generation in animal models. However, further work is required to understand the role of HMGB1 and its isoforms in epileptogenesis and drug resistance. Using a combination of animal models and sera from clinically well-characterized patients, we have demonstrated that there are dynamic changes in HMGB1 isoforms in the brain and blood of animals undergoing epileptogenesis. The pathologic disulfide HMGB1 isoform progressively increased in blood before epilepsy onset and prospectively identified animals that developed the disease. Consistent with animal data, we observed early expression of disulfide HMGB1 in patients with newly diagnosed epilepsy, and its persistence was associated with subsequent seizures. In contrast with patients with well-controlled epilepsy, patients with chronic, drug-refractory epilepsy persistently expressed the acetylated, disulfide HMGB1 i...Continue Reading

References

Mar 1, 1972·Electroencephalography and Clinical Neurophysiology·R J Racine
Aug 18, 2000·The European Journal of Neuroscience·M G De SimoniA Vezzani
Jul 12, 2002·Nature·Paola ScaffidiMarco E Bianchi
Apr 17, 2003·Journal of Endotoxin Research·Huan YangKevin J Tracey
Oct 9, 2003·The EMBO Journal·Tiziana BonaldiMarco E Bianchi
Mar 1, 2005·Journal of Leukocyte Biology·Huan YangKevin J Tracey
Aug 9, 2007·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Simon R ClarkNancy J Rothwell
May 15, 2008·Brain : a Journal of Neurology·Francesco NoèAnnamaria Vezzani
Oct 28, 2008·Brain : a Journal of Neurology·Silvia BalossoAnnamaria Vezzani
Nov 19, 2008·QJM : Monthly Journal of the Association of Physicians·M-H TsaiC-H Lu
Sep 29, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Daniel J AntoineB Kevin Park
Aug 31, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mohamed LamkanfiVishva M Dixit
Dec 8, 2010·Nature Reviews. Neurology·Annamaria VezzaniTallie Z Baram
Jan 12, 2011·Annual Review of Immunology·Ulf Andersson, Kevin J Tracey
Mar 19, 2011·Brain : a Journal of Neurology·Emanuele ZuroloEleonora Aronica
Mar 1, 2012·The Journal of Experimental Medicine·Milena SchiraldiMariagrazia Uguccioni
Apr 3, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Helena ParfenovaCharles W Leffler
Aug 2, 2012·Nature Reviews. Drug Discovery·Charles A DinarelloJos W M van der Meer
Aug 8, 2012·The Journal of Experimental Medicine·Emilie VenereauMarco E Bianchi
Mar 14, 2013·Protein & Cell·Ben LuKevin J Tracey
Feb 5, 2014·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Asla Pitkänen, Jerome Engel
Jun 3, 2014·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yu OkumaMasahiro Nishibori
Jun 15, 2014·The Journal of Biological Chemistry·Xiaodong GeNatalia Nieto
Jul 12, 2014·Advances in Experimental Medicine and Biology·Ray DingledineF Edward Dudek
Jan 9, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Michael D WeberSteven F Maier

❮ Previous
Next ❯

Citations

Apr 24, 2017·Neurochemical Research·Annamaria VezzaniTeresa Ravizza
Feb 11, 2018·Molecular Neurobiology·Federica FrigerioChristophe Bernard
Aug 26, 2018·Journal of Neurochemistry·Fabrizio MichettiMaria Concetta Geloso
May 30, 2019·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Luqiao HuangChunbao Guo
Oct 12, 2018·Cellular and Molecular Life Sciences : CMLS·Angela RaucciMaurizio C Capogrossi
Jun 27, 2019·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·Minchen KanPingping Fang
Jul 18, 2019·Frontiers in Neurology·Dominik KobylarekWojciech Kozubski
Jan 22, 2020·BMC Veterinary Research·Eva-Lotta von RüdenHeidrun Potschka
Feb 16, 2018·Expert Opinion on Therapeutic Targets·Ulf AnderssonHelena Harris
Jun 12, 2020·Epilepsia Open·Pablo M Casillas-EspinosaTerence J O'Brien
May 1, 2019·The Journal of Clinical Investigation·Marion C HoggJochen Hm Prehn
Jun 26, 2020·Frontiers in Neurology·Johanna RuhnauAntje Vogelgesang
Oct 12, 2018·Brain : a Journal of Neurology·Federica FrigerioAnnamaria Vezzani
Oct 28, 2018·Nature Communications·Shin MuraiHiroyasu Nakano
Jun 22, 2019·Current Gene Therapy·Jingjing ZhaoYufeng Liu
Nov 4, 2020·Immunity, Inflammation and Disease·Bo LiKai Le
Nov 6, 2020·Journal of Veterinary Internal Medicine·Yoonhoi KooByeong-Teck Kang
Sep 10, 2019·Neuropharmacology·Pavel Klein, Ivana Tyrlikova
Aug 3, 2020·Life Sciences·Ishnoor KaurSandeep Arora
Nov 28, 2017·Brain, Behavior, and Immunity·Kristina A KigerlPhillip G Popovich
Mar 22, 2021·Epilepsy & Behavior : E&B·Najib KissaniMusa Watila
Dec 12, 2018·Pharmacology & Therapeutics·Laura PellegriniFederica Limana
Jul 6, 2021·Aging and Disease·Batool F KirmaniRobert J Delorenzo
Jan 24, 2020·ACS Chemical Neuroscience·Yam Nath PaudelMohd Farooq Shaikh
Sep 21, 2021·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Cuilian YeChunbao Guo

❮ Previous
Next ❯

Methods Mentioned

BETA
acetylation
ELISA

Software Mentioned

TWin
Clampfit
GraphPad Prism

Related Concepts

Related Feeds

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here

Related Papers

Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics
Sandy R ShultzRuben Kuzniecky
The New England Journal of Medicine
P Kwan, M J Brodie
© 2022 Meta ULC. All rights reserved