Inflammation and Oxidative Stress in Multiple Sclerosis: Consequences for Therapy Development

CNS inflammation is a major driver of MS pathology. Differential immune responses, including the adaptive and the innate immune system, are observed at various stages of MS and drive disease development and progression. Next to these immune-mediated mechanisms, other mediators contribute to MS pathology. These include immune-independent cell death of oligodendrocytes and neurons as well as oxidative stress-induced tissue damage. In particular, the complex influence of oxidative stress on inflammation and vice versa makes therapeutic interference complex. All approved MS therapeutics work by modulating the autoimmune response. However, despite substantial developments in the treatment of the relapsing-remitting form of MS, approved therapies for the progressive forms of MS as well as for MS-associated concomitants are limited and much needed. Here, we summarize the contribution of inflammation and oxidative stress to MS pathology and discuss consequences for MS therapy development.

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Dimethyl Fumarate and Its Esters: A Drug with Broad Clinical Utility?

Pharmaceuticals ◽

10.3390/ph13100306 ◽

2020 ◽

Vol 13 (10) ◽

pp. 306 ◽

Cited By ~ 2

Author(s):

Stephanie Kourakis ◽

Cara A. Timpani ◽

Judy B. de Haan ◽

Nuri Gueven ◽

Dirk Fischer ◽

...

Keyword(s):

Oxidative Stress ◽

Dimethyl Fumarate ◽

Immune Mediated ◽

Relapsing Remitting ◽

Favourable Safety ◽

Potential Benefits ◽

Monomethyl Fumarate ◽

Relapsing Remitting Multiple Sclerosis ◽

And Oxidative Stress ◽

Acid Esters

Fumaric acid esters (FAEs) are small molecules with anti-oxidative, anti-inflammatory and immune-modulating effects. Dimethyl fumarate (DMF) is the best characterised FAE and is approved and registered for the treatment of psoriasis and Relapsing-Remitting Multiple Sclerosis (RRMS). Psoriasis and RRMS share an immune-mediated aetiology, driven by severe inflammation and oxidative stress. DMF, as well as monomethyl fumarate and diroximel fumarate, are commonly prescribed first-line agents with favourable safety and efficacy profiles. The potential benefits of FAEs against other diseases that appear pathogenically different but share the pathologies of oxidative stress and inflammation are currently investigated.

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Dimethyl Fumarate and Its Esters: A Drug with Broad Clinical Utility?

10.20944/preprints202009.0684.v1 ◽

2020 ◽

Author(s):

Stephanie Kourakis ◽

Cara Timpani ◽

Judy de Haan ◽

Nuri Gueven ◽

Dirk Fischer ◽

...

Keyword(s):

Oxidative Stress ◽

Dimethyl Fumarate ◽

Immune Mediated ◽

Relapsing Remitting ◽

Favourable Safety ◽

Potential Benefits ◽

Monomethyl Fumarate ◽

Relapsing Remitting Multiple Sclerosis ◽

And Oxidative Stress ◽

Acid Esters

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Rumen-protected methionine supplementation during the peripartal period alters the expression of galectin genes associated with inflammation in peripheral neutrophils and secretion in plasma of Holstein cows

Journal of Dairy Research ◽

10.1017/s0022029919000736 ◽

2019 ◽

Vol 86 (4) ◽

pp. 394-398

Author(s):

Emmanuel K. Asiamah ◽

Mario Vailati-Riboni ◽

Zheng Zhou ◽

Tianle Xu ◽

Juan J. Loor ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Dietary Intervention ◽

Innate Immune ◽

Signaling Cascades ◽

Surface Receptors ◽

Il Interleukin ◽

Periparturient Period ◽

Methionine Supplementation ◽

And Oxidative Stress

AbstractThe work described in this research communication aimed to investigate whether rumen-protected methionine (Met) supplementation during the periparturient period would affect the expression of galectins in blood-derived neutrophils, and secretion of galectins, IL (interleukin)-1β, IL-6, myeloperoxidase (MPO), and glucose in plasma. Because supplementation of rumen-protected Met would alleviate inflammation and oxidative stress during the peripartal period, we hypothesized that enhancing Met supply would benefit the innate immune response at least in part by altering the expression of galectin genes associated with neutrophil activity and inflammation. Galectins (Gal) have an immuno-modulating effect acting like cell-surface receptors whose activation often results in signaling cascades stimulating cells such as neutrophils. This study revealed an association between Met supplementation and galectin expression and secretion. This implies that galectin expression and secretion can be modulated by Met supplementation. Further studies are needed to evaluate the regulation of galectin gene expression for therapeutic and dietary intervention in the peripartal cow.

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Spontaneous Prematurity, Innate Immune System, and Oxidative Stress at the Maternal-Fetal Interface: An Overview

Translational Studies on Inflammation ◽

10.5772/intechopen.88379 ◽

2020 ◽

Author(s):

Natália Prearo Moço ◽

Bruna Ribeiro de Andrade Ramos ◽

Mariana de Castro Silva ◽

Jossimara Polettini ◽

Ramkumar Menon ◽

...

Keyword(s):

Oxidative Stress ◽

Immune System ◽

Innate Immune System ◽

Innate Immune ◽

And Oxidative Stress ◽

Maternal Fetal Interface

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Relapsing Remitting Multiple Sclerosis and its Relationship with the Immune System and Oxidative Stress

Current Immunology Reviews ◽

10.2174/1573395514666171226154300 ◽

2018 ◽

Vol 14 (1) ◽

pp. 15-23

Author(s):

Ada Paloma Soto-Brambila ◽

Genaro Gabriel Ortiz ◽

Paloma Rivero-Moragrega ◽

Ana Laura Briones-Torres ◽

Luis Javier Gonzalez-Ortiz ◽

...

Keyword(s):

Oxidative Stress ◽

Multiple Sclerosis ◽

Immune System ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Relapsing Remitting Multiple Sclerosis ◽

And Oxidative Stress

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The Importance of Redox Status in the Frame of Lifestyle Approaches and the Genetics of the Lung Innate Immune Molecules, SP-A1 and SP-A2, on Differential Outcomes of COVID-19 Infection

Antioxidants ◽

10.3390/antiox9090784 ◽

2020 ◽

Vol 9 (9) ◽

pp. 784 ◽

Cited By ~ 2

Author(s):

Fotios Tekos ◽

Zoi Skaperda ◽

Nikolaos Goutzourelas ◽

David S. Phelps ◽

Joanna Floros ◽

...

Keyword(s):

Oxidative Stress ◽

Protein A ◽

The Elderly ◽

Redox Balance ◽

Surfactant Protein ◽

Redox Status ◽

Innate Immune ◽

Differential Outcomes ◽

Underlying Diseases ◽

And Oxidative Stress

The pandemic of COVID-19 is of great concern to the scientific community. This mainly affects the elderly and people with underlying diseases. People with obesity are more likely to experience unpleasant disease symptoms and increased mortality. The severe oxidative environment that occurs in obesity due to chronic inflammation permits viral activation of further inflammation leading to severe lung disease. Lifestyle affects the levels of inflammation and oxidative stress. It has been shown that a careful diet rich in antioxidants, regular exercise, and fasting regimens, each and/or together, can reduce the levels of inflammation and oxidative stress and strengthen the immune system as they lead to weight loss and activate cellular antioxidant mechanisms and reduce oxidative damage. Thus, a lifestyle change based on the three pillars: antioxidants, exercise, and fasting could act as a proactive preventative measure against the adverse effects of COVID-19 by maintaining redox balance and well-functioning immunity. Moreover, because of the observed diversity in the expression of COVID-19 inflammation, the role of genetics of innate immune molecules, surfactant protein A (SP-A)1 and SP-A2, and their differential impact on the local lung microenvironment and host defense is reviewed as genetics may play a major role in the diverse expression of the disease.

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