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

Several neuroactive metabolites of the kynurenine pathway of tryptophan deg radation have been speculatively linked to the pathophysiology of Huntingto n's Disease (HD). Here we demonstrate that the levels of two of these metab olites, the free radical generator 3-hydroxykynurenine (3HK) and the neurop rotectant kynurenate (KYNA), are increased in the neostriatum of stage 1 HD patients and in the brain of mice transgenic for full-length mutant huntin gtin. In both cases, the elevation in 3HK was far more pronounced, resultin g in significant increases in the 3HK/KYNA ratios. These data suggest that abnormal kynurenine pathway metabolism may play a role during the early pha ses of the neurodegenerative process in HD. (C) 2000 Elsevier Science Irela nd Ltd. All rights reserved.