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International Journal of Tryptophan Research

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Quinolinic Acid, an Endogenous Molecule Combining Excitotoxicity, Oxidative Stress and Other Toxic Mechanisms

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Publication Date: 23 Feb 2012

Type: Review

Journal: International Journal of Tryptophan Research

Citation: International Journal of Tryptophan Research 2012:5 1-8

doi: 10.4137/IJTR.S8158

Abstract

Quinolinic acid (QUIN), an endogenous metabolite of the kynurenine pathway, is involved in several neurological disorders, including Huntington's disease, Alzheimer's disease, schizophrenia, HIV associated dementia (HAD) etc. QUIN toxicity involves several mechanisms which trigger various metabolic pathways and transcription factors. The primary mechanism exerted by this excitotoxin in the central nervous system (CNS) has been largely related with the overactivation of N-methyl-D-aspartate receptors and increased cytosolic Ca2+ concentrations, followed by mitochondrial dysfunction, cytochrome c release, ATP exhaustion, free radical formation and oxidative damage. As a result, this toxic pattern is responsible for selective loss of middle size striatal spiny GABAergic neurons and motor alterations in lesioned animals. This toxin has recently gained attention in biomedical research as, in addition to its proven excitotoxic profile, a considerable amount of evidence suggests that oxidative stress and energetic disturbances are major constituents of its toxic pattern in the CNS. Hence, this profile has changed our perception of how QUIN-related disorders combine different toxic mechanisms resulting in brain damage. This review will focus on the description and integration of recent evidence supporting old and suggesting new mechanisms to explain QUIN toxicity.


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What Your Colleagues Say About International Journal of Tryptophan Research
My experience with Int J Tryptophan Research has been excellent. The editors and reviewers were most helpful and very "open" intellectually given we were proposing a novel and counter-intuitive hypothesis. The administrative staff have been patient, quick, helpful and friendly. I would and have recommended this group of journals to colleagues.
Dr Adrian Williams (University Hospitals Birmingham, Birmingham, UK)
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