L-kynurenine: metabolism and mechanism of neuroprotection

Abstract

L-kynurenine is an intermediate in the pathway of the metabolism of L-tryptophan to nicotinic acid. L-kynurenine is formed in the mammalian brain (40%) and is taken up from the periphery (60%), indicating that it can be transported across the BBB. It was discovered some 30 years ago that compounds in the kynurenine family have neuroactive properties. L-kynurenine, the central agent of this pathway, can be converted into two other important compounds: the neuroprotective kynurenic acid and the neurotoxic quinolinic acid. Kynurenines have been shown to be involved in many diverse physiological and pathological processes. There are a number of neurodegenerative disorders whose pathogenesis has been demonstrated to involve multiple imbalances of the kynurenine pathway metabolism. This review summarizes the main steps of the kynurenine pathway under normal conditions, discusses the metabolic disturbances and changes in this pathway in certain neurodegenerative disorders, and finally introduces the therapeutic possibilities with kynurenines.