Abstract
Kynurenic acid, a metabolite of the tryptophan-NAD pathway, acts as antagonist for both the α7 nicotinic acetylcholine receptor and glycine co-agonist sites of the N-methyl-D-aspartic acid receptor at endogenous brain concentrations. Elevation of brain kynurenic acid levels reduces the release of neurotransmitters and deficits cognitive functions in experimental animals. Patients of schizophrenia and bipolar disorder show higher kynurenic acid levels in their brain and cerebrospinal cortex. Therefore, it is considered that kynurenic acid is involved in psychiatric disorders such as schizophrenia and depression. The control of the kynurenine pathway, especially kynurenic acid production, in the brain is an important target for improvement of brain function or effective treatment of brain disorders. Several factors such as high tryptophan diet, stress, type 1 diabetes, and acute liver failure increase brain kynurenic acid levels, whereas kynurenine aminotransferase inhibitor and exercise can inhibit elevation of brain kynurenic acid levels. Recent studies have suggested the possibility that amino acids may suppress kynurenic acid production via blockade of kynurenine transport or inhibition of kynurenic acid synthesis reactions. This approach may be useful in the treatment and prevention of neurological and psychiatric diseases associated with elevated kynurenic acid levels.
