The
kynurenine pathway is a major route of
L-tryptophan catabolism producing neuroactive metabolites implicated in neurodegeneration and immune tolerance. We characterized the
kynurenine pathway in human neurons and the human SK-N-SH
neuroblastoma cell line and found that the
kynurenine pathway
enzymes were variably expressed. Picolinic carboxylase was expressed only in primary and some adult neurons but not in SK-N-SH cells. Because of this difference, SK-N-SH cells were able to produce the
excitotoxin quinolinic acid, whereas human neurons produced the
neuroprotectant picolinic acid. The net result of
kynurenine pathway induction in human neurons is therefore predicted to result in neuroprotection, immune regulation, and
tumor inhibition, whereas in SK-N-SH cells, it may result in neurotoxicity, immune tolerance, and
tumor promotion. This study represents the first comprehensive characterization of the
kynurenine pathway in neurons and the first description of the involvement of the
kynurenine pathway as a mechanism for controlling both
tumor cell neurotoxicity and persistence.