Inhibiting the kynurenine pathway in spinal cord injury: multiple therapeutic potentials?

Kelly R. Jacobs, David B. Lovejoy*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    15 Citations (Scopus)
    53 Downloads (Pure)

    Abstract

    Chronic induction of the kynurenine pathway (KP) contributes to neuroinflammation by producing the excitotoxin quinolinic acid (QUIN). This has led to significant interest in the development of inhibitors of this pathway, particularly in the context of neurodegenerative disease. However, acute spinal cord injury (SCI) also results in deleterious increases in QUIN, as secondary inflammatory processes mediated largely by infiltrating macrophages, become predominant. QUIN mediates significant neurotoxicity primarily by excitotoxic stimulation of the N-methyl-D-aspartate receptor, but other mechanisms of QUIN toxicity are known. More recent focus has assessed the contribution that neuroinflammation and modulations in the KP make in mood and psychiatric disorders with recent studies linking inflammation and modulations in the KP, to impaired cognitive performance and depressed mood in SCI patients. We hypothesize that these findings suggest that in SCI, inhibition of QUIN production and other metabolites, may have multiple therapeutic modalities and further studies investigating this are warranted. However, for central nervous system-based conditions, achieving good blood-brain-barrier permeability continues to be a limitation of current KP inhibitors.

    Original languageEnglish
    Pages (from-to)2073-2076
    Number of pages4
    JournalNeural Regeneration Research
    Volume13
    Issue number12
    DOIs
    Publication statusPublished - 1 Dec 2018

    Bibliographical note

    Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

    Keywords

    • activated microglia
    • depression
    • infiltrating macrophages
    • kynurenine pathway
    • neuroinflammation
    • neuropsychiatry
    • quinolinic acid
    • spinal cord injury

    Fingerprint

    Dive into the research topics of 'Inhibiting the kynurenine pathway in spinal cord injury: multiple therapeutic potentials?'. Together they form a unique fingerprint.

    Cite this