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

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

doi:10.1016/S0304-3940(00)00956-3

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 journal › Article › peer-review

90 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 language	English (US)
Pages (from-to)	233-235
Number of pages	3
Journal	Neuroscience Letters
Volume	283
Issue number	3
DOIs	https://doi.org/10.1016/S0304-3940(00)00956-3
State	Published - Apr 14 2000
Externally published	Yes

Keywords

3-Hydroxykynurenine
Excitotoxicity
Free radicals
Huntingtin
Kynurenic acid
Neurodegeneration

ASJC Scopus subject areas

Neuroscience(all)

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10.1016/S0304-3940(00)00956-3

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title = "Early kynurenergic impairment in Huntington's Disease and in a transgenic animal model",

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.",

keywords = "3-Hydroxykynurenine, Excitotoxicity, Free radicals, Huntingtin, Kynurenic acid, Neurodegeneration",

author = "Paolo Guidetti and {Hemachandra Reddy}, P. and Tagle, {Danilo A.} and Robert Schwarcz",

note = "Funding Information: We thank Dr R. McMahon for help with the statistical analysis and Mrs Joyce Burgess for excellent secretarial assistance. This work was supported by USPHS grants NS 28236 (to RS) and MH/NS 31862 (Harvard Brain Tissue Resource Center), a grant from the Hereditary Disease Foundation (to DAT), and a fellowship from the Huntington's Disease Society of America (to PHR).",

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AU - Hemachandra Reddy, P.

AU - Tagle, Danilo A.

AU - Schwarcz, Robert

N1 - Funding Information: We thank Dr R. McMahon for help with the statistical analysis and Mrs Joyce Burgess for excellent secretarial assistance. This work was supported by USPHS grants NS 28236 (to RS) and MH/NS 31862 (Harvard Brain Tissue Resource Center), a grant from the Hereditary Disease Foundation (to DAT), and a fellowship from the Huntington's Disease Society of America (to PHR).

PY - 2000/4/14

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N2 - 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.

AB - 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.

KW - 3-Hydroxykynurenine

KW - Excitotoxicity

KW - Free radicals

KW - Huntingtin

KW - Kynurenic acid

KW - Neurodegeneration

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

Abstract

Keywords

ASJC Scopus subject areas

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