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

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Guillemin, Gilles J., Kerr, Stephen J., Smythe, George A., Smith, Danielle G., Kapoor, Vimal, Armati, Patricia J., Croitoru, Juliana, Brew, Bruce J.·2001·Journal of Neurochemistry
DOI 10.1046/j.1471-4159.2001.00498.x
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Abstract

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.

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Metadata

Authors
Guillemin, G. J., Kerr, S. J., Smythe, G. A., Smith, D. G., Kapoor, V., Armati, P. J., Croitoru, J., & Brew, B. J.
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2001-08-15
Volume
78
Issue
4
Pages
842-853
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
DOI
10.1046/j.1471-4159.2001.00498.x
OpenAlex
W1547937746
Cited by
538
References
1
FWCI
3.55
Type
journal article
Language
en
Open access
bronze
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 127 d)

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CoChat. (2026). Citation check: Kynurenine pathway metabolism in human astrocytes: a paradox for neuronal protection. https://app.cochat.ai/papers/10.1046/j.1471-4159.2001.00498.x
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Guillemin, G. J., Kerr, S. J., Smythe, G. A., Smith, D. G., Kapoor, V., Armati, P. J., Croitoru, J., & Brew, B. J. (2001). Kynurenine pathway metabolism in human astrocytes: a paradox for neuronal protection. Journal of Neurochemistry. https://doi.org/10.1046/j.1471-4159.2001.00498.x

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