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Life Sci. 2019 Dec 1;238:116924. doi: 10.1016/j.lfs.2019.116924. Epub 2019 Oct 10.

High mobility group box 1 (HMGB1) protein in Multiple Sclerosis (MS): Mechanisms and therapeutic potential.

Author information

1
Neuropharmacology Research Laboratory, 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.
3
School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia.
4
Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: cpiperi@med.uoa.gr.
5
Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia. Electronic address: Iekhsan.othman@monash.edu.

Abstract

Multiple sclerosis (MS) is an autoimmune chronic inflammatory disease with distinctive features of focal demyelination, axonal loss, activation of glial cells, and immune cells infiltration. The precise molecular mechanism underlying the disease progression remains enigmatic despite of the rapid progression on experimental and clinical MS research. The focus of MS therapy relies on the repression of the pathogenic autoimmune response without compromising an adaptive immune response. High mobility group box-1 (HMGB1) protein is a ubiquitous nuclear protein driving pro-inflammatory responses as well as targeting innate immune signaling that initiates and mediates autoimmunity as well as sterile injury. A considerable amount of experimental and human studies suggests the contribution of HMGB1 in the pathogenesis of MS/experimental autoimmune encephalitis (EAE). In this regard, HMGB1 protein has gained increased attention, as an emerging possible therapeutic target against MS. This is more strengthened by the promising therapeutic outcome demonstrated by HMGB1 neutralizing agents in the experimental EAE model. Herein, we attempt to shed more light on the molecular crosstalk of HMGB1 protein in the pathogenesis of MS/EAE suggesting that HMGB1 blockade could impede the pro-inflammatory loop that drives MS autoimmunity.

KEYWORDS:

Demyelination; Experimental autoimmune encephalomyelitis; HMGB1; Inflammation; Multiple sclerosis

PMID:
31606383
DOI:
10.1016/j.lfs.2019.116924
[Indexed for MEDLINE]

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