Abstract
Multiple sclerosis (MS) has been considered for a long time a typical inflammatory demyelinating disease of the central nervous system due to autoimmunity targeting oligodendrocytes with sparing of axons until advanced stages of the disease. For this reason, most of the earliest experimental studies focused on the role of cytokines and chemokines at the site of oligodendrocytes loss and on the importance in MS pathogenesis of classical inflammatory mechanisms. As a result, several attempts to treat MS through reduction of the local inflammatory milieau have been performed, leading to the current “immunomodulatory” treatment of the disease. However, more recently the importance of axonal loss and neurodegeneration even in the earliest stages of MS has been also recognized, and additional or concomitant players have been therefore searched. Evidence is now increasing that excessive glutamate is released at the site of demyelination and axonal degeneration in MS plaques, and the most probable candidates for this cellular release are infiltrating leukocytes and activated microglia. These observations are no longer simply preclinical results obtained in the MS animal model, i.e. experimental allergic encephalomyelitis, but have already been partially confirmed by post-mortem studies and in vivo analysis in MS patients, thus raising the possibility that modulation of glutamate release and transport as well as receptors blockade might be relevant targets for the development of future therapeutic interventions.
Keywords: Glutamate, multiple sclerosis, neurodegeneration, inflammation, demyelination, post-mortem studies, immunomodulatory, encephalomyelitis, glutamatergic
Current Medicinal Chemistry
Title: Glutamate and Multiple Sclerosis
Volume: 19 Issue: 9
Author(s): M. Frigo, M. G. Cogo, M. L. Fusco, M. Gardinetti and B. Frigeni
Affiliation:
Keywords: Glutamate, multiple sclerosis, neurodegeneration, inflammation, demyelination, post-mortem studies, immunomodulatory, encephalomyelitis, glutamatergic
Abstract: Multiple sclerosis (MS) has been considered for a long time a typical inflammatory demyelinating disease of the central nervous system due to autoimmunity targeting oligodendrocytes with sparing of axons until advanced stages of the disease. For this reason, most of the earliest experimental studies focused on the role of cytokines and chemokines at the site of oligodendrocytes loss and on the importance in MS pathogenesis of classical inflammatory mechanisms. As a result, several attempts to treat MS through reduction of the local inflammatory milieau have been performed, leading to the current “immunomodulatory” treatment of the disease. However, more recently the importance of axonal loss and neurodegeneration even in the earliest stages of MS has been also recognized, and additional or concomitant players have been therefore searched. Evidence is now increasing that excessive glutamate is released at the site of demyelination and axonal degeneration in MS plaques, and the most probable candidates for this cellular release are infiltrating leukocytes and activated microglia. These observations are no longer simply preclinical results obtained in the MS animal model, i.e. experimental allergic encephalomyelitis, but have already been partially confirmed by post-mortem studies and in vivo analysis in MS patients, thus raising the possibility that modulation of glutamate release and transport as well as receptors blockade might be relevant targets for the development of future therapeutic interventions.
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Cite this article as:
Frigo M., G. Cogo M., L. Fusco M., Gardinetti M. and Frigeni B., Glutamate and Multiple Sclerosis, Current Medicinal Chemistry 2012; 19 (9) . https://dx.doi.org/10.2174/092986712799462559
DOI https://dx.doi.org/10.2174/092986712799462559 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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