Early kynurenergic impairment in Huntington's Disease and in a transgenic animal model

Paolo Guidetti, P. Hemachandra Reddy, Danilo A. Tagle, Robert Schwarcz

    Research output: Contribution to journalArticle

    76 Scopus citations

    Abstract

    Several neuroactive metabolites of the kynurenine pathway of tryptophan degradation have been speculatively linked to the pathophysiology of Huntington's Disease (HD). Here we demonstrate that the levels of two of these metabolites, the free radical generator 3-hydroxykynurenine (3HK) and the neuroprotectant kynurenate (KYNA), are increased in the neostriatum of stage 1 HD patients and in the brain of mice transgenic for full-length mutant huntingtin. In both cases, the elevation in 3HK was far more pronounced, resulting in significant increases in the 3HK/KYNA ratios. These data suggest that abnormal kynurenine pathway metabolism may play a role during the early phases of the neurodegenerative process in HD. Copyright (C) 2000 Elsevier Science Ireland Ltd.

    Original languageEnglish (US)
    Pages (from-to)233-235
    Number of pages3
    JournalNeuroscience Letters
    Volume283
    Issue number3
    DOIs
    StatePublished - Apr 14 2000

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    Keywords

    • 3-Hydroxykynurenine
    • Excitotoxicity
    • Free radicals
    • Huntingtin
    • Kynurenic acid
    • Neurodegeneration

    ASJC Scopus subject areas

    • Neuroscience(all)

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