Tóth Fanni, Fülöp Ferenc, Szatmári István, Toldi József, Dékány Imre, Vécsei László
Általános Orvostudományi Kar, Szent-Györgyi Albert Klinikai Központ, Interdiszciplináris Kiválósági Központ, Neurológiai Klinika,Szegedi TudományegyetemSzeged, Semmelweis u. 6., 6725.
Gyógyszerésztudományi Kar, Interdiszciplináris Kiválósági Központ, Gyógyszerkémiai Intézet,Szegedi TudományegyetemSzeged.
Orv Hetil. 2020 Mar;161(12):443-451. doi: 10.1556/650.2020.31673.
Currently kynurenines are considered a hot topic, because of their involvement in numerous physiological and pathological processes. The essential amino acid, tryptophan's main metabolism is through the kynurenine pathway. During the degradation of tryptophan, kynurenic acid is formed with the help of kynurenine aminotransferases. Kynurenic acid is an excitatory receptor ligand and it possesses neuroprotective properties. Abnormal decrease or increase in the kynurenic acid level can cause an imbalance in the neurotransmitter systems and it is associated with several neurodegenerative and neuropsychiatric disorders. Kynurenic acid has a poor penetration through the blood-brain barrier, so it is unfit for therapeutic purposes. For this reason, the aim of our research was the synthesis and pharmacological testing of kynurenic acid analogues with a better blood-brain barrier penetration. The newly synthetized kynurenic acid analogues proved to be effective in models of some nervous system disorders (migraine, Huntington's disease). According to our results with the novel kynurenic acid analogues, these molecules may represent a new therapeutic target in the treatment of neurodegenerative diseases. Several patent applications were filed based on our results. Orv Hetil. 2020; 161(12): 443-451.
目前，犬尿氨酸因其参与众多生理和病理过程而被视为一个热门话题。必需氨基酸色氨酸的主要代谢途径是通过犬尿氨酸途径。在色氨酸降解过程中，犬尿氨酸转氨酶会帮助生成犬尿酸。犬尿酸是一种兴奋性受体配体，具有神经保护特性。犬尿酸水平的异常降低或升高会导致神经递质系统失衡，并与多种神经退行性疾病和神经精神疾病相关。犬尿酸通过血脑屏障的穿透性较差，因此不适合用于治疗目的。出于这个原因，我们研究的目的是合成具有更好血脑屏障穿透性的犬尿酸类似物并进行药理测试。新合成的犬尿酸类似物在一些神经系统疾病（偏头痛、亨廷顿舞蹈症）模型中被证明是有效的。根据我们对新型犬尿酸类似物的研究结果，这些分子可能代表了神经退行性疾病治疗中的一个新的治疗靶点。基于我们的研究结果，已提交了多项专利申请。《匈牙利医学周报》。2020年；161(12): 443 - 451。
