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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
High mobility group box 1 (HMGB1) protein in Multiple Sclerosis (MS): Mechanisms and therapeutic potential
Yam Nath Paudel1, Efthalia Angelopoulou2, Bhuvan K C3
1Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia.
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.
Insights
High mobility group box-1 (HMGB1) protein fuels multiple sclerosis (MS) inflammation. Blocking HMGB1 may impede the autoimmune disease
Area of Science:
- Neuroimmunology
- Autoimmune Diseases
- Molecular Mechanisms
Background:
- Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease characterized by demyelination and axonal loss.
- The exact molecular drivers of MS progression are not fully understood.
- Current MS therapies aim to suppress the autoimmune response without harming adaptive immunity.
Purpose of the Study:
- To explore the role of High mobility group box-1 (HMGB1) protein in the pathogenesis of MS and its animal model, experimental autoimmune encephalitis (EAE).
- To evaluate HMGB1 as a potential therapeutic target for MS.
- To elucidate the molecular interactions of HMGB1 in MS autoimmunity.
Main Methods:
- Review of experimental and human studies on HMGB1 in MS/EAE.
- Analysis of HMGB1's role in innate immune signaling and pro-inflammatory responses.
- Assessment of therapeutic outcomes using HMGB1 neutralizing agents in EAE models.
Main Results:
- HMGB1 protein is implicated in initiating and mediating autoimmune responses and sterile injury.
- Studies suggest HMGB1 contributes significantly to the pathogenesis of MS and EAE.
- HMGB1 neutralizing agents have shown promising therapeutic effects in experimental EAE.
Conclusions:
- HMGB1 protein plays a crucial role in the pro-inflammatory loop driving MS autoimmunity.
- Targeting HMGB1 represents a potential therapeutic strategy for multiple sclerosis.
- Blocking HMGB1 may effectively impede the autoimmune processes underlying MS.
