Neuroprotection by kynurenine metabolites

Abstract

The overexcitation of excitatory amino acid receptors generates excitotoxicity, which plays an important role in the pathophysiology of various neurodegenerative disorders such as Parkinson's and Alzheimer's diseases, stroke, and epilepsy. The prevention of excitotoxic neuronal damage is therefore a major objective in neuroprotective strategies. The kynurenine pathway, the main route of the tryptophan metabolism, produces both neuroprotective and neurotoxic metabolites. Kynurenic acid is a broad-spectrum endogenous antagonist of ionotropic excitatory amino acid receptors, and hence it can prevent excitotoxic neuronal damage. The kynurenine metabolites are additionally involved in the regulation of glutamatergic and cholinergic neurotransmission. The pathogeneses of several neurodegenerative disorders have been shown to involve multiple imbalances in the kynurenine metabolism. Kynurenine pathway metabolites may provide important targets for future neuroprotective therapeutic strategies.