Role of dimethyl fumarate in oxidative stress of multiple sclerosis: A review

Suneetha, A.; Rajeswari, K. Raja

doi:10.1016/j.jchromb.2016.02.010

Cited by 28 publications

(8 citation statements)

References 77 publications

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“…MS is a disease of neuroinflammation and neurodegeneration, thus the ability to influence neuronal or glial survival and the inflammatory state specifically within the CNS are critical components to consider for any MS therapy. DMF has long been known to protect cells facing oxidative stress through the activation of nuclear factor erythroid-2-related factor (Nrf2) from studies aimed at determining the mechanism related to its benefit for psoriasis patients ( 61 ). DMF-mediated induction of the Nrf2-ERK1/2 MAPK pathway leads to the increased expression of various antioxidant proteins such as HO-1, glutathione-S-transferase, superoxide dismutase, and quinone oxidoreductase-1 in various cell types ( 62 – 65 ).…”

Section: Mechanism Of Action In Cnsmentioning

confidence: 99%

Emerging Understanding of the Mechanism of Action for Dimethyl Fumarate in the Treatment of Multiple Sclerosis

et al. 2018

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Dimethyl fumarate (DMF) is an effective treatment option for relapsing–remitting multiple sclerosis (MS), but its therapeutic mechanism of action has not been fully elucidated. A better understanding of its mechanism will allow for the development of assays to monitor its clinical efficacy and safety in patients, as well as guide the development of the next generation of therapies for MS. In order to build the foundation for determining its mechanism, we reviewed the manner in which DMF alters lymphocyte subsets in MS patients, its impact on clinical efficacy and safety, as well as its molecular effects in cellular and animal models. DMF decreases absolute lymphocyte counts, but does not affect all subsets uniformly. CD8+ T-cells are the most profoundly affected, but reduction also occurs in the CD4+ population, particularly within the pro-inflammatory T-helper Th1 and Th17 subsets, creating a bias toward more anti-inflammatory Th2 and regulatory subsets. Similarly, B-lymphocyte, myeloid, and natural killer populations are also shifted toward a more anti-inflammatory state. In vitro and animal models demonstrate a role for DMF within the central nervous system (CNS) in promoting neuronal survival in an Nrf2 pathway-dependent manner. However, the impact of DMF directly within the CNS of MS patients remains largely unknown.

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Section: Mechanism Of Action In Cnsmentioning

confidence: 99%

Emerging Understanding of the Mechanism of Action for Dimethyl Fumarate in the Treatment of Multiple Sclerosis

et al. 2018

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“…Additionally, NO x creates a family of toxic molecules known as RNS. Finally, it leads to nitrosylation resulting in cellular death [3]. High levels of NO x are implicated in active MS lesions produced by astrocytes and microglia, as an after-effect of the expression of iNOS.…”

Section: Discussionmentioning

confidence: 99%

“…However, DMTs are suspected to downregulate inflammatory cytokines and reduce blood-brain barrier permeability and T-cell migration into the CNS. The second-line agents (e.g., NT monoclonal antibody) decrease inflammatory response by blocking receptors on white blood cells which allow them to enter the brain and the spinal cord [3]. Fingolimod is able to interfere with the inflammatory phase of MS through the prevention of lymphocyte infiltration into the CNS [34].…”

Section: Discussionmentioning

confidence: 99%

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Assessment of Serum Nitrogen Species and Inflammatory Parameters in Relapsing-Remitting Multiple Sclerosis Patients Treated with Different Therapeutic Approaches

Niedziela

Adamczyk-Sowa

Niedziela

et al. 2016

BioMed Research International

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The role of nitric oxide and its reactive derivatives (NOx) is well known in the pathogenesis of multiple sclerosis, which is an inflammatory disease while NOx seems to be important in coordinating inflammatory response. The purpose of the present study was to assess serum NOx as one of the nitrogen species and inflammatory parameters in relapsing-remitting multiple sclerosis patients and to compare the effectiveness of various types of disease-modifying therapies that reduce nitric oxide and inflammatory biomarkers. Elevated NOx level was observed in patients who received the first-line disease-modifying therapy (interferons beta-1a and beta-1b) in comparison with the subjects treated with the second-line disease-modifying therapy (natalizumab; fingolimod) and healthy controls without significant differences in C-reactive protein and interleukin-1 beta. A negative correlation was observed between serum NOx level and the duration of multiple sclerosis confirmed in the whole study population and in subjects treated with the first-line agents. Only serum NOx, concentration could reveal a potential efficacy of disease-modifying therapy with a better reduction in NOx level due to the second-line agents of disease-modifying therapy.

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“…DMF and monomethyl fumarate (MMF) activate Nrf2 transcriptional pathways (97). Target genes of Nrf2 include heme oxygenase-1, glutamate cysteine ligase transcription factor1, and NAD(P)H oxidoreductase-1.…”

Section: The Relationship Between Immunomodulatory Therapy Os and Amentioning

confidence: 99%

Novel Approaches of Oxidative Stress Mechanisms in the Multiple Sclerosis Pathophysiology and Therapy

Adamczyk

Niedziela

Adamczyk-Sowa

2017

Multiple Sclerosis: Perspectives in Treatment and Pathogenesis

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Abstract:It is suspected that the development of multiple sclerosis (MS) can be affected by oxidative stress (OS). In the acute phase of the disease, OS is responsible for initiating inflammation, whereas in the chronic phase it sustains neurodegenerative process. Redox processes in MS are related to dysregulation of axonal bioenergetics, cerebral iron accumulation, mitochondrial dysfunction, impaired oxidant/antioxidant balance, and OS memory. This chapter gives an overview of the role of OS in MS.

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Role of dimethyl fumarate in oxidative stress of multiple sclerosis: A review

Cited by 28 publications

References 77 publications

Emerging Understanding of the Mechanism of Action for Dimethyl Fumarate in the Treatment of Multiple Sclerosis

Emerging Understanding of the Mechanism of Action for Dimethyl Fumarate in the Treatment of Multiple Sclerosis

Assessment of Serum Nitrogen Species and Inflammatory Parameters in Relapsing-Remitting Multiple Sclerosis Patients Treated with Different Therapeutic Approaches

Novel Approaches of Oxidative Stress Mechanisms in the Multiple Sclerosis Pathophysiology and Therapy

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