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 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Genetically Modified Animals
Huntington Disease
Kynurenic Acid
Kynurenine
Animal Models
Neostriatum
Neuroprotective Agents
Tryptophan
Transgenic Mice
Free Radicals
Brain
3-hydroxykynurenine

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Early kynurenergic impairment in Huntington's Disease and in a transgenic animal model. / Guidetti, Paolo; Reddy, P (Hemachandra); Tagle, Danilo A.; Schwarcz, Robert.

In: Neuroscience Letters, Vol. 283, No. 3, 14.04.2000, p. 233-235.

Research output: Contribution to journalArticle

Guidetti, Paolo ; Reddy, P (Hemachandra) ; Tagle, Danilo A. ; Schwarcz, Robert. / Early kynurenergic impairment in Huntington's Disease and in a transgenic animal model. In: Neuroscience Letters. 2000 ; Vol. 283, No. 3. pp. 233-235.
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