New insights into tryptophan metabolism in ischemic stroke: A promising therapeutic target

Ischemic stroke is a major cause of disability and mortality worldwide. Dysregulation of tryptophan metabolism has been increasingly implicated in its pathophysiology. Tryptophan is catabolized through three principal pathways: the kynurenine, serotonin, and microbial indole pathways, each producing bioactive metabolites that modulate neuroinflammation, oxidative stress, excitotoxicity, and immune responses following stroke. An elevated quinolinic acid/kynurenic acid ratio reflects enhanced neurotoxicity, while alterations in gut-derived indole metabolites impair gut-brain signaling. This review highlights key enzymes-IDO, TDO, TPH-and receptors such as AHR as potential therapeutic targets. Although preclinical studies are promising, clinical translation remains challenging due to metabolic complexity, blood-brain barrier limitations, and individual variability in gut microbiota. Future research should integrate multi-omics technologies and well-designed clinical trials to develop targeted therapies for ischemic stroke.