Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/11618
Title: Neostriatal and cortical quinolinate levels are increased in early grade Huntington's disease.
Authors: Guidetti, P
Luthi-Carter, RE
Augood, SJ
Schwarcz, R
First Published: Dec-2004
Citation: NEUROBIOL DIS, 2004, 17 (3), pp. 455-461
Abstract: Huntington's disease (HD), an inherited neurodegenerative disorder, is caused by an abnormal polyglutamine expansion in the huntingtin protein. This genetic defect may result in heightened neuronal susceptibility to excitotoxic injury, a mechanism that has been postulated to play a critical role in HD. Quinolinate (QUIN) and kynurenate (KYNA), two endogenous neuroactive metabolites of the kynurenine pathway of tryptophan degradation, have been proposed to modulate excitotoxic neuronal death in HD. A third kynurenine pathway metabolite, the free radical generator 3-hydroxykynurenine (3-HK), has also been hypothesized to play a causal role in the pathogenesis of HD. We show here that the brain levels of both 3-HK and QUIN are increased three to four-fold in low-grade (grade 0/1) HD brain. These changes were seen in the neocortex and in the neostriatum, but not in the cerebellum. In contrast, brain 3-HK and QUIN levels were either unchanged or tended to decrease in grade 2 and advanced grade (grades 3-4) HD brain. Brain kynurenine and KYNA levels fluctuated only modestly as the illness progressed. These results support a possible involvement of 3-HK and QUIN in the early phases of HD pathophysiology and indicate novel therapeutic strategies against the disease.
DOI Link: 10.1016/j.nbd.2004.07.006
ISSN: 0969-9961
Links: http://hdl.handle.net/2381/11618
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Cell Physiology and Pharmacology

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