Though migraine and neurodegenerative disorders have a high socioeconomic impact, their therapeutic
management has not been fully addressed. Their pathomechanisms are not completely understood, but glutamateinduced
excitotoxicity, mitochondrial disturbances and oxidative stress all seem to play crucial roles. The overactivation
of glutamate receptors contributes to the hyperexcitability observed in migraine and also to the neurodegenerative
process. The kynurenine pathway of the tryptophan metabolism produces the only known endogenous Nmethyl-
D-aspartate receptor antagonist, kynurenic acid, which has been proven in different preclinical studies to
exert a neuroprotective effect. Influencing the kynurenine pathway might be beneficial in migraine and neurodegenerative
diseases, and in the normalization of glutamatergic neurotransmission and the prevention of excitotoxic neuronal damage. The
synthesis of kynurenic acid analogues may offer a valuable tool for drug development.
Keywords: Migraine, hyperexcitability, neurodegeneration, neuroprotection, kynurenic acid, kynurenic acid analogues.
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