Kynurenine pathway metabolism in human astrocytes: A paradox for neuronal protection

Gilles J. Guillemin*, Stephen J. Kerr, George A. Smythe, Danielle G. Smith, Vimal Kapoor, Patricia J. Armati, Juliana Croitoru, Bruce J. Brew

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

356 Citations (Scopus)


There is good evidence that the kynurenine pathway (KP) and one of its products, quinolinic acid (QUIN), play a role in the pathogenesis of neurological diseases, in particular AIDS dementia complex. Although QUIN has been shown to be produced in neurotoxic concentrations by macrophages and microglia, the role of astrocytes in QUIN production is controversial. Using cytokine-stimulated cultures of human astrocytes, we assayed key enzymes and products of the KP. We found that human astrocytes lack kynurenine hydroxylase so that large amounts of kynurenine and the QUIN antagonist kynurenic acid were produced. However, the amounts of QUIN that were synthesized were subsequently completely degraded. We then showed that kynurenine in concentrations comparable with those produced by astrocytes led to significant production of QUIN by macrophages. These results suggest that astrocytes alone are neuroprotective by minimizing QUIN production and maximizing synthesis of kynurenic acid. However, it is likely that, in the presence of macrophages and/or microglia, astrocytes become indirectly neurotoxic by the production of large concentrations of kynurenine that can be secondarily metabolized by neighbouring or infiltrating monocytic cells to form the neurotoxin QUIN.

Original languageEnglish
Pages (from-to)842-853
Number of pages12
JournalJournal of Neurochemistry
Issue number4
Publication statusPublished - 2001
Externally publishedYes


  • Human astrocyte
  • Kynurenine
  • Kynurenine pathway
  • Neurotoxicity
  • Quinolinic acid

Fingerprint Dive into the research topics of 'Kynurenine pathway metabolism in human astrocytes: A paradox for neuronal protection'. Together they form a unique fingerprint.

Cite this