TY  - JOUR
AU  - Miljković, Đorđe
AU  - Blazevski, Jana
AU  - Petković, Filip
AU  - Djedović, Neda
AU  - Momcilović, Miljana
AU  - Stanisavljević, Suzana
AU  - Jevtic, Bojan
AU  - Mostarica-Stojković, Marija
AU  - Spasojević, Ivan
PY  - 2015
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/891
AB  - Dimethyl fumarate (DMF), a new drug for multiple sclerosis (MS) treatment, acts against neuroinflammation via mechanisms that are triggered by adduct formation with thiol redox switches. Ethyl pyruvate (EP), an off-the-shelf agent, appears to be a redox analog of DMF, but its immunomodulatory properties have not been put into the context of MS therapy. In this article, we examined and compared the effects of EP and DMF on MS-relevant activity/functions of T cells, macrophages, microglia, and astrocytes. EP efficiently suppressed the release of MS signature cytokines, IFN-gamma and IL-17, from human PBMCs. Furthermore, the production of these cytokines was notably decreased in encephalitogenic T cells after in vivo application of EP to rats. Production of two other proinflammatory cytokines, IL-6 and TNF, and NO was suppressed by EP in macrophages and microglia. Reactive oxygen species production in macrophages, microglia activation, and the development of Ag-presenting phenotype in microglia and macrophages were constrained by EP. The release of IL-6 was reduced in astrocytes. Finally, EP inhibited the activation of transcription factor NF-kappa B in microglia and astrocytes. Most of these effects were also found for DMF, implying that EP and DMF share common targets and mechanisms of action. Importantly, EP had in vivo impact on experimental autoimmune encephalomyelitis, an animal model of MS. Treatment with EP resulted in delay and shortening of the first relapse, and lower clinical scores, whereas the second attack was annihilated. Further studies on the possibility to use EP as an MS therapeutic are warranted.
PB  - Amer Assoc Immunologists, Bethesda
T2  - Journal of Immunology
T1  - A Comparative Analysis of Multiple Sclerosis-Relevant Anti-Inflammatory Properties of Ethyl Pyruvate and Dimethyl Fumarate
EP  - 2503
IS  - 6
SP  - 2493
VL  - 194
DO  - 10.4049/jimmunol.1402302
ER  - 

@article{
author = "Miljković, Đorđe and Blazevski, Jana and Petković, Filip and Djedović, Neda and Momcilović, Miljana and Stanisavljević, Suzana and Jevtic, Bojan and Mostarica-Stojković, Marija and Spasojević, Ivan",
year = "2015",
abstract = "Dimethyl fumarate (DMF), a new drug for multiple sclerosis (MS) treatment, acts against neuroinflammation via mechanisms that are triggered by adduct formation with thiol redox switches. Ethyl pyruvate (EP), an off-the-shelf agent, appears to be a redox analog of DMF, but its immunomodulatory properties have not been put into the context of MS therapy. In this article, we examined and compared the effects of EP and DMF on MS-relevant activity/functions of T cells, macrophages, microglia, and astrocytes. EP efficiently suppressed the release of MS signature cytokines, IFN-gamma and IL-17, from human PBMCs. Furthermore, the production of these cytokines was notably decreased in encephalitogenic T cells after in vivo application of EP to rats. Production of two other proinflammatory cytokines, IL-6 and TNF, and NO was suppressed by EP in macrophages and microglia. Reactive oxygen species production in macrophages, microglia activation, and the development of Ag-presenting phenotype in microglia and macrophages were constrained by EP. The release of IL-6 was reduced in astrocytes. Finally, EP inhibited the activation of transcription factor NF-kappa B in microglia and astrocytes. Most of these effects were also found for DMF, implying that EP and DMF share common targets and mechanisms of action. Importantly, EP had in vivo impact on experimental autoimmune encephalomyelitis, an animal model of MS. Treatment with EP resulted in delay and shortening of the first relapse, and lower clinical scores, whereas the second attack was annihilated. Further studies on the possibility to use EP as an MS therapeutic are warranted.",
publisher = "Amer Assoc Immunologists, Bethesda",
journal = "Journal of Immunology",
title = "A Comparative Analysis of Multiple Sclerosis-Relevant Anti-Inflammatory Properties of Ethyl Pyruvate and Dimethyl Fumarate",
pages = "2503-2493",
number = "6",
volume = "194",
doi = "10.4049/jimmunol.1402302"
}

Miljković, Đ., Blazevski, J., Petković, F., Djedović, N., Momcilović, M., Stanisavljević, S., Jevtic, B., Mostarica-Stojković, M.,& Spasojević, I.. (2015). A Comparative Analysis of Multiple Sclerosis-Relevant Anti-Inflammatory Properties of Ethyl Pyruvate and Dimethyl Fumarate. in Journal of Immunology
Amer Assoc Immunologists, Bethesda., 194(6), 2493-2503.
https://doi.org/10.4049/jimmunol.1402302

Miljković Đ, Blazevski J, Petković F, Djedović N, Momcilović M, Stanisavljević S, Jevtic B, Mostarica-Stojković M, Spasojević I. A Comparative Analysis of Multiple Sclerosis-Relevant Anti-Inflammatory Properties of Ethyl Pyruvate and Dimethyl Fumarate. in Journal of Immunology. 2015;194(6):2493-2503.
doi:10.4049/jimmunol.1402302 .

Miljković, Đorđe, Blazevski, Jana, Petković, Filip, Djedović, Neda, Momcilović, Miljana, Stanisavljević, Suzana, Jevtic, Bojan, Mostarica-Stojković, Marija, Spasojević, Ivan, "A Comparative Analysis of Multiple Sclerosis-Relevant Anti-Inflammatory Properties of Ethyl Pyruvate and Dimethyl Fumarate" in Journal of Immunology, 194, no. 6 (2015):2493-2503,
https://doi.org/10.4049/jimmunol.1402302 . .

TY  - JOUR
AU  - Miljković, Đorđe
AU  - Spasojević, Ivan
PY  - 2013
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/731
AB  - The pathophysiology of multiple sclerosis (MS) involves several components: redox, inflammatory/autoimmune, vascular, and neurodegenerative. All of them are supported by the intertwined lines of evidence, and none of them should be written off. However, the exact mechanisms of MS initiation, its development, and progression are still elusive, despite the impressive pace by which the data on MS are accumulating. In this review, we will try to integrate the current facts and concepts, focusing on the role of redox changes and various reactive species in MS. Knowing the schedule of initial changes in pathogenic factors and the key turning points, as well as understanding the redox processes involved in MS pathogenesis is the way to enable MS prevention, early treatment, and the development of therapies that target specific pathophysiological components of the heterogeneous mechanisms of MS, which could alleviate the symptoms and hopefully stop MS. Pertinent to this, we will outline (i) redox processes involved in MS initiation; (ii) the role of reactive species in inflammation; (iii) prooxidative changes responsible for neurodegeneration; and (iv) the potential of antioxidative therapy. Antioxid. Redox Signal. 19, 2286-2334.
PB  - Mary Ann Liebert, Inc, New Rochelle
T2  - Antioxidants & Redox Signaling
T1  - Multiple Sclerosis: Molecular Mechanisms and Therapeutic Opportunities
EP  - 2334
IS  - 18
SP  - 2286
VL  - 19
DO  - 10.1089/ars.2012.5068
ER  - 

@article{
author = "Miljković, Đorđe and Spasojević, Ivan",
year = "2013",
abstract = "The pathophysiology of multiple sclerosis (MS) involves several components: redox, inflammatory/autoimmune, vascular, and neurodegenerative. All of them are supported by the intertwined lines of evidence, and none of them should be written off. However, the exact mechanisms of MS initiation, its development, and progression are still elusive, despite the impressive pace by which the data on MS are accumulating. In this review, we will try to integrate the current facts and concepts, focusing on the role of redox changes and various reactive species in MS. Knowing the schedule of initial changes in pathogenic factors and the key turning points, as well as understanding the redox processes involved in MS pathogenesis is the way to enable MS prevention, early treatment, and the development of therapies that target specific pathophysiological components of the heterogeneous mechanisms of MS, which could alleviate the symptoms and hopefully stop MS. Pertinent to this, we will outline (i) redox processes involved in MS initiation; (ii) the role of reactive species in inflammation; (iii) prooxidative changes responsible for neurodegeneration; and (iv) the potential of antioxidative therapy. Antioxid. Redox Signal. 19, 2286-2334.",
publisher = "Mary Ann Liebert, Inc, New Rochelle",
journal = "Antioxidants & Redox Signaling",
title = "Multiple Sclerosis: Molecular Mechanisms and Therapeutic Opportunities",
pages = "2334-2286",
number = "18",
volume = "19",
doi = "10.1089/ars.2012.5068"
}

Miljković, Đ.,& Spasojević, I.. (2013). Multiple Sclerosis: Molecular Mechanisms and Therapeutic Opportunities. in Antioxidants & Redox Signaling
Mary Ann Liebert, Inc, New Rochelle., 19(18), 2286-2334.
https://doi.org/10.1089/ars.2012.5068

Miljković Đ, Spasojević I. Multiple Sclerosis: Molecular Mechanisms and Therapeutic Opportunities. in Antioxidants & Redox Signaling. 2013;19(18):2286-2334.
doi:10.1089/ars.2012.5068 .

Miljković, Đorđe, Spasojević, Ivan, "Multiple Sclerosis: Molecular Mechanisms and Therapeutic Opportunities" in Antioxidants & Redox Signaling, 19, no. 18 (2013):2286-2334,
https://doi.org/10.1089/ars.2012.5068 . .