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*

*Corresponding author for this work

    Research output: Contribution to journalArticle

    34 Citations (Scopus)
    22 Downloads (Pure)

    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.

    Original languageEnglish
    Article number204
    Pages (from-to)1-11
    Number of pages11
    JournalJournal of Neuroinflammation
    Volume11
    DOIs
    Publication statusPublished - 13 Dec 2014

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