Tajti Janos, Majlath Zsofia, Szok Delia, Csati Anett, Toldi Jozsef, Fulop Ferenc, Vecsei Laszlo
Department of Neurology, University of Szeged, Faculty of Medicine, Albert Szent-Gyorgyi Clinical Centre, Semmelweis u. 6. H-6725 Szeged, Hungary.
Curr Pharm Des. 2015;21(17):2250-8. doi: 10.2174/1381612821666150105163055.
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.
尽管偏头痛和神经退行性疾病具有很高的社会经济影响，但其治疗管理尚未得到充分解决。它们的发病机制尚未完全明确，但谷氨酸诱导的兴奋性毒性、线粒体紊乱和氧化应激似乎都起着关键作用。谷氨酸受体的过度激活导致偏头痛中观察到的过度兴奋，也导致神经退行性过程。色氨酸代谢的犬尿氨酸途径产生唯一已知的内源性N-甲基-D-天冬氨酸受体拮抗剂犬尿喹啉酸，在不同的临床前研究中已证明其具有神经保护作用。影响犬尿氨酸途径可能对偏头痛和神经退行性疾病有益，有助于谷氨酸能神经传递正常化并预防兴奋性毒性神经元损伤。犬尿喹啉酸类似物的合成可能为药物开发提供有价值的工具。
