Review Article Quinolinic Acid: An Endogenous Neurotoxin with Multiple Targets

Copyright © 2013 Rafael Lugo-Huitrón et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Quinolinic acid (QUIN), a neuroactivemetabolite of the kynurenine pathway, is normally presented in nanomolar concentrations in human brain and cerebrospinal fluid (CSF) and is often implicated in the pathogenesis of a variety of human neurological diseases. QUIN is an agonist of N-methyl-D-aspartate (NMDA) receptor, and it has a high in vivo potency as an excitotoxin. In fact, although QUIN has an uptake system, its neuronal degradation enzyme is rapidly saturated, and the rest of extracellular QUIN can continue stimulating the NMDA receptor. However, its toxicity cannot be fully explained by its activation of NMDA receptors it is likely that additional mechanisms may also be involved. In this review we describe some of the most relevant targets of QUIN neurotoxicity which involves presynaptic receptors, energetic dysfunction, oxidative stress, transcription factors, cytoskeletal disruption, behavior alterations, and cell death. 1. Biosynthesis of Quinolinic Acid (QUIN) Tryptophan (TRP) is an essential amino acid that has various important biological functions. In mammals, about 90 % of dietary TRP is metabolized along the kynurenine pathwa