Quinolinic acid toxicity on oligodendroglial cells: Relevance for multiple sclerosis and therapeutic strategies

Gayathri Sundaram, Bruce J. Brew, Simon P. Jones, Seray Adams, Chai K. Lim, Gilles J. Guillemin

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    The excitotoxin quinolinic acid, a by-product of the kynurenine pathway, is known to be involved in several neurological diseases including multiple sclerosis (MS). Quinolinic acid levels are elevated in experimental autoimmune encephalomyelitis rodents, the widely used animal model of MS. Our group has also found pathophysiological concentrations of quinolinic acid in MS patients. This led us to investigate the effect of quinolinic acid on oligodendrocytes; the main cell type targeted by the autoimmune response in MS. We have examined the kynurenine pathway (KP) profile of two oligodendrocyte cell lines and show that these cells have a limited threshold to catabolize exogenous quinolinic acid. We further propose and demonstrate two strategies to limit quinolinic acid gliotoxicity: 1) by neutralizing quinolinic acid's effects with anti-quinolinic acid monoclonal antibodies and 2) directly inhibiting quinolinic acid production from activated monocytic cells using specific KP enzyme inhibitors. The outcome of this study provides a new insight into therapeutic strategies for limiting quinolinic acid-induced neurodegeneration, especially in neurological disorders that target oligodendrocytes, such as MS.

    LanguageEnglish
    Article number204
    Pages1-11
    Number of pages11
    JournalJournal of Neuroinflammation
    Volume11
    DOIs
    Publication statusPublished - 13 Dec 2014

    Fingerprint

    Quinolinic Acid
    Multiple Sclerosis
    Kynurenine
    Oligodendroglia
    Therapeutics
    Autoimmune Experimental Encephalomyelitis
    Neurotoxins
    Enzyme Inhibitors
    Nervous System Diseases
    Autoimmunity
    Rodentia
    Animal Models
    Monoclonal Antibodies
    Outcome Assessment (Health Care)
    Cell Line

    Bibliographical note

    This version is archived for private and non-commercial use under the terms of this BioMed Central open access license ("license") (see http://www.biomedcentral.com/about/license). The work is protected by copyright and/or other applicable law. Any use of the work other than as authorized under this license is prohibited. For further rights please check the terms of the license, or contact the publisher.

    Cite this

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    title = "Quinolinic acid toxicity on oligodendroglial cells: Relevance for multiple sclerosis and therapeutic strategies",
    abstract = "The excitotoxin quinolinic acid, a by-product of the kynurenine pathway, is known to be involved in several neurological diseases including multiple sclerosis (MS). Quinolinic acid levels are elevated in experimental autoimmune encephalomyelitis rodents, the widely used animal model of MS. Our group has also found pathophysiological concentrations of quinolinic acid in MS patients. This led us to investigate the effect of quinolinic acid on oligodendrocytes; the main cell type targeted by the autoimmune response in MS. We have examined the kynurenine pathway (KP) profile of two oligodendrocyte cell lines and show that these cells have a limited threshold to catabolize exogenous quinolinic acid. We further propose and demonstrate two strategies to limit quinolinic acid gliotoxicity: 1) by neutralizing quinolinic acid's effects with anti-quinolinic acid monoclonal antibodies and 2) directly inhibiting quinolinic acid production from activated monocytic cells using specific KP enzyme inhibitors. The outcome of this study provides a new insight into therapeutic strategies for limiting quinolinic acid-induced neurodegeneration, especially in neurological disorders that target oligodendrocytes, such as MS.",
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    Quinolinic acid toxicity on oligodendroglial cells : Relevance for multiple sclerosis and therapeutic strategies. / Sundaram, Gayathri; Brew, Bruce J.; Jones, Simon P.; Adams, Seray; Lim, Chai K.; Guillemin, Gilles J.

    In: Journal of Neuroinflammation, Vol. 11, 204, 13.12.2014, p. 1-11.

    Research output: Contribution to journalArticleResearchpeer-review

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    AU - Lim,Chai K.

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