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Licensed Unlicensed Requires Authentication Published by De Gruyter November 12, 2012

Multiple sclerosis and glutamate excitotoxicity

  • Milos Kostic

    Dr. Milos S. Kostic, currently a PhD student, is working as a teaching assistant at the Department of Immunology, Faculty of Medicine, University of Nis. His ongoing PhD thesis explores Th immunological profile of patients suffering from multiple sclerosis and its repercussion on neurodegenerative processes in the form of axonal degeneration. Major scientific interest is Th17 polarized environment in encephalic compartment and its association with glutamate excitotoxicity.

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    , Nikola Zivkovic

    Dr. Nikola D. Zivkovic is employed as a teaching assistant at the Department of Pathology, Faculty of Medicine, University of Nis. Currently a PhD student, engaged in research in the field of immunoproliferative diseases. His special interest is head and neck pathology with focus on disorders of immune system in this region.

    and Ivana Stojanovic

    Prof. Dr. Ivana R. Stojanovic received a PhD in Biochemistry at University of Nis Faculty of Medicine on polyamine and nitric oxide metabolism interactions in seizures. The leader of the scientific subproject, exploring L-arginine metabolism and nitric oxide signalling in CNS inflammation and neurodegeneration. Her current scientific interests focus on the role of oxidative stress, nitrergicsignalling and excitotoxicity in multiple sclerosis pathogenetic mechanisms.

Abstract

The previous understanding of multiple sclerosis was solely related to neuroinflammation and its harmful effects; however, countless data indicate the importance of some inflammation-independent, neurodegenerative mechanisms associated with mitochondria malfunction, iron deposition and oxidative stress. Recently, it has been postulated that glutamate excitotoxicity, a phenomenon that takes place when an excessive amount of glutamate overactivates its cellular receptors and induces cell death, could be a missing link between inflammatory and neurodegenerative processes evident in multiple sclerosis. Glutamate is the major excitatory neurotransmitter of the central nervous system, which has been proven to have a central role in a complex communication network established between all residential brain cells, including neurons, astrocytes, oligodendrocytes and microglia. Thus, the disturbance of glutamate homeostasis could affect practically all physiological functions and interactions of brain cells, leading to heterogeneity of pathological events. The understanding of glutamate excitotoxicity as a valid mechanism of central nervous system damage in multiple sclerosis, requires the revision of the current knowledge about a source of elevated extracellular glutamate, glutamate receptor alterations, alterations of glutamate transporters and metabolizing enzymes, as well as molecular mechanism of excitotoxic damage.


Corresponding author: Milos Kostic, Departement of Immunology, Faculty of Medicine, University of Nis, 18000 Nis, Serbia

About the authors

Milos Kostic

Dr. Milos S. Kostic, currently a PhD student, is working as a teaching assistant at the Department of Immunology, Faculty of Medicine, University of Nis. His ongoing PhD thesis explores Th immunological profile of patients suffering from multiple sclerosis and its repercussion on neurodegenerative processes in the form of axonal degeneration. Major scientific interest is Th17 polarized environment in encephalic compartment and its association with glutamate excitotoxicity.

Nikola Zivkovic

Dr. Nikola D. Zivkovic is employed as a teaching assistant at the Department of Pathology, Faculty of Medicine, University of Nis. Currently a PhD student, engaged in research in the field of immunoproliferative diseases. His special interest is head and neck pathology with focus on disorders of immune system in this region.

Ivana Stojanovic

Prof. Dr. Ivana R. Stojanovic received a PhD in Biochemistry at University of Nis Faculty of Medicine on polyamine and nitric oxide metabolism interactions in seizures. The leader of the scientific subproject, exploring L-arginine metabolism and nitric oxide signalling in CNS inflammation and neurodegeneration. Her current scientific interests focus on the role of oxidative stress, nitrergicsignalling and excitotoxicity in multiple sclerosis pathogenetic mechanisms.

Received: 2012-8-2
Accepted: 2012-9-7
Published Online: 2012-11-12
Published in Print: 2013-02-01

©2013 by Walter de Gruyter Berlin Boston

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