Briefly, through a series of enzymatic steps, tryptophan is normally converted into kynurenine, then to 3-hydroxykynurenine via kynurenine 3-monooxygenase (KMO; B2, NAD[P.sup.+]), then 3-hydroxyanthranilic acid is formed by kynureninase (KYNU; B6), and proceeds down the pathway to become either acetyl-coA, picolinic acid or quinolinic acid
, which is further converted into NA[D.sup.+] through another series of enzymatic steps.
The hyperactivity of the enzymes subsequently increase the catabolism of tryptophan via the KP, which results in the production of neuro-active metabolites, of which quinolinic acid
(QUIN) had the most detrimental effects .
Brew, "Implications for the kynurenine pathway and quinolinic acid
in amyotrophic lateral sclerosis," Neurodegenerative Diseases, vol.
Heyes, "A mechanism for increased quinolinic acid
formation following acute systemic immune stimulation," The Journal of Biological Chemistry, vol.
Gos et al., "Severe depression is associated with increased microglial quinolinic acid
in subregions of the anterior cingulate gyrus: evidence for an immunemodulated glutamatergic neurotransmission?" Journal of Neuroinflammation, vol.
The results also showed decreased quinolinic acid
levels among a subset of patients who came back six months later, when their suicidal behavior had ended.
Statins have been shown to be neuroprotective in a group of animal disease models and clinical studies.11,17 Statins are shown to prevent hippocampal neuron death in kainic acid (KA), pilocarpine, pentylentetrasole and quinolinic acid
(QA)-induced epileptic seizures.11,13
Citation: "Mesenchymal stem cells induced to secrete neurotrophic factors attenuate quinolinic acid
toxicity: A potential therapy for Huntington's disease;" Sadan etal.; Experimental Neurology, available online 19 January 2012.
Our group has described protective and antioxidant properties of SAC in different animal models of neurotoxicity, including models in rats induced by the glutamate analogue quinolinic acid
(Perez-Severiano et al.
kynurenine, quinolinic acid
(Quin) or kynurenic acid (Kyna).
The resulting metabolite, kynurenine, can be converted to KYNA or further metabolized to produce quinolinic acid
, an NMDA agonist.
Administration of recombinant human Activin-A has powerful neurotrophic effects on select striatal phenotypes in the quinolinic acid
lesion model of Huntington's disease.