Dimethyl Fumarate (Tecfidera)

Venci, Jineane V.; Gandhi, Mona A.

doi:10.1177/1060028013509232

Cited by 39 publications

(10 citation statements)

References 18 publications

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“…To do this, we utilized the fumaric acid ester monomethyl fumarate (MMF). MMF is the active metabolite of dimethyl fumarate, which is now approved for treatment of multiple sclerosis (69, 70). Importantly, we have previously shown that MMF successfully ameliorates ROS accumulation and antiretroviral-induced toxicity in neuroglial cell cultures (32).…”

Section: Resultsmentioning

confidence: 99%

Altered Oligodendrocyte Maturation and Myelin Maintenance: The Role of Antiretrovirals in HIV-Associated Neurocognitive Disorders

Jensen

Monnerie

Mannell

et al. 2015

J Neuropathol Exp Neurol

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Despite effective viral suppression through combined antiretroviral therapy (cART), approximately half of HIV-positive individuals suffer from HIV-Associated Neurocognitive Disorders (HAND). Studies of antiretroviral treated patients have revealed persistent white matter pathologies including diffuse myelin pallor, diminished white matter tracts, and decreased myelin protein mRNAs. Loss of myelin can contribute to neurocognitive dysfunction as the myelin membrane generated by oligodendrocytes is essential for rapid signal transduction and axonal maintenance. We hypothesized that myelin changes in HAND are partly due to effects of antiretroviral drugs on oligodendrocyte survival and/or maturation. We showed that primary mouse oligodendrocyte precursor cell cultures treated with therapeutic concentrations of HIV protease inhibitors Ritonavir or Lopinavir displayed dose-dependent decreases in oligodendrocyte maturation; however, this effect was rapidly reversed following drug removal. Conversely, nucleoside reverse transcriptase inhibitor Zidovudine had no effect. Furthermore, in vivo Ritonavir administration to adult mice reduced frontal cortex myelin protein levels. Finally, prefrontal cortex tissue from HIV-positive individuals with HAND on cART showed a significant decrease in myelin basic protein compared with untreated HIV-positive individuals with HAND or HIV-negative controls. These findings demonstrate that antiretrovirals can impact myelin integrity, and have implications for myelination in juvenile HIV patients, and myelin maintenance in adults on lifelong therapy.

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Section: Resultsmentioning

confidence: 99%

Altered Oligodendrocyte Maturation and Myelin Maintenance: The Role of Antiretrovirals in HIV-Associated Neurocognitive Disorders

Jensen

Monnerie

Mannell

et al. 2015

J Neuropathol Exp Neurol

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“…In 2013 dimethyl fumarate (Tecfidera) was approved by the FDA as a first-line therapy for adults with relapsing MS, although its mechanism of action remains largely unknown [55] . α-NETA and dimethyl fumarate share certain features such as small size (242 Da and 144 Da, respectively) and simplicity in structure.…”

Section: Discussionmentioning

confidence: 99%

A Novel CMKLR1 Small Molecule Antagonist Suppresses CNS Autoimmune Inflammatory Disease

et al. 2014

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Therapies that target leukocyte trafficking pathways can reduce disease activity and improve clinical outcomes in multiple sclerosis (MS). Experimental autoimmune encephalomyelitis (EAE) is a widely studied animal model that shares many clinical and histological features with MS. Chemokine-like receptor-1 (CMKLR1) is a chemoattractant receptor that is expressed by key effector cells in EAE and MS, including macrophages, subsets of dendritic cells, natural killer cells and microglia. We previously showed that CMKLR1-deficient (CMKLR1 KO) mice develop less severe clinical and histological EAE than wild-type mice. In this study, we sought to identify CMKLR1 inhibitors that would pharmaceutically recapitulate the CMKLR1 KO phenotype in EAE. We identified 2-(α-naphthoyl) ethyltrimethylammonium iodide (α-NETA) as a CMKLR1 small molecule antagonist that inhibits chemerin-stimulated β-arrestin2 association with CMKLR1, as well as chemerin-triggered CMKLR1+ cell migration. α-NETA significantly delayed the onset of EAE induced in C57BL/6 mice by both active immunization with myelin oligodendrocyte glycoprotein peptide 35-55 and by adoptive transfer of encephalitogenic T cells. In addition, α-NETA treatment significantly reduced mononuclear cell infiltrates within the CNS. This study provides additional proof-of-concept data that targeting CMKLR1:chemerin interactions may be beneficial in preventing or treating MS.

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“…Currently DMF is approved by the FDA to treat patients with relapsing multiple sclerosis (MS). Other NRF2 activators are also being investigated in clinical trials for a variety of diseases [107, 108]. Sulforaphane (SFN) is an isothiocyanate that is naturally present in cruciferous vegetables such as broccoli and cabbage.…”

Section: Modulation Of Nrf2 Signaling: Nrf2 Activatorsmentioning

confidence: 99%

Dual roles of NRF2 in tumor prevention and progression: Possible implications in cancer treatment

Moon

Giaccia

2015

Free Radical Biology and Medicine

144

112

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The Cap’N’Collar (CNC) family serves as cellular sensors of oxidative and electrophilic stresses and shares structural similarities including basic leucine zipper (bZIP) and CNC domains,. They form heterodimers with small MAF proteins to regulate antioxidant and phase II enzymes through antioxidant response element (ARE)-mediated transactivation. Among the CNC family members, NRF2 is required for systemic protection against redox-mediated injury and carcinogenesis. On the other hand, NRF2 is activated by oncogenic pathways, metabolism, and hypoxia. Constitutive NRF2 activation is observed in a variety of human cancers and it is highly correlated with tumor progression and aggressiveness. In this review, we will discuss how NRF2 plays dual roles in cancer prevention and progression depending on the cellular context and environment. Therefore, a better understanding of NRF2 will be necessary to exploit this complex network of balancing antioxidant pathways to inhibit tumor progression.

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Dimethyl Fumarate (Tecfidera)

Cited by 39 publications

References 18 publications

Altered Oligodendrocyte Maturation and Myelin Maintenance: The Role of Antiretrovirals in HIV-Associated Neurocognitive Disorders

Altered Oligodendrocyte Maturation and Myelin Maintenance: The Role of Antiretrovirals in HIV-Associated Neurocognitive Disorders

A Novel CMKLR1 Small Molecule Antagonist Suppresses CNS Autoimmune Inflammatory Disease

Dual roles of NRF2 in tumor prevention and progression: Possible implications in cancer treatment

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