Németh H, Toldi J, Vécsei L
Department of Neurology, University of Szeged, Hungary.
J Neural Transm Suppl. 2006(70):285-304. doi: 10.1007/978-3-211-45295-0_45.
The kynurenine pathway is the main pathway of tryptophan metabolism. L-kynurenine is a central compound of this pathway since it can change to the neuroprotective agent kynurenic acid or to the neurotoxic agent quinolinic acid. The break-up of these endogenous compounds' balance can be observable in many disorders. It can be occur in neurodegenerative disorders, such as Parkinson's disease, Huntington's and Alzheimer's disease, in stroke, in epilepsy, in multiple sclerosis, in amyotrophic lateral sclerosis, and in mental failures, such as schizophrenia and depression. The increase of QUIN concentration or decrease of KYNA concentration could enhance the symptoms of several diseases. According to numerous studies, lowered KYNA level was found in patients with Parkinson's disease. It can be also noticeable that KYNA-treatment prevents against the QUIN-induced lesion of rat striatum in animal experiments. Administrating of KYNA can be appear a promising therapeutic approach, but its use is limited because of its poorly transport across the blood-brain barrier. The solution may be the development of KYNA analogues (e.g. glucoseamine-kynurenic acid) which can pass across this barrier and disengaging in the brain, then KYNA can exert its neuroprotective effects binding at the excitatory glutamate receptors, in particular the NMDA receptors. Furthermore, it seems hopeful to use kynurenine derivatives (e.g. 4-chloro-kynurenine) or enzyme inhibitors (e.g. Ro-61-8048) to ensure an increased kynurenic acid concentration in the central nervous system.
犬尿氨酸途径是色氨酸代谢的主要途径。L-犬尿氨酸是该途径的核心化合物，因为它可以转变为神经保护剂犬尿酸或神经毒素喹啉酸。这些内源性化合物平衡的破坏在许多疾病中都可以观察到。它可发生于神经退行性疾病，如帕金森病、亨廷顿病和阿尔茨海默病，中风、癫痫、多发性硬化症、肌萎缩侧索硬化症，以及精神障碍，如精神分裂症和抑郁症。喹啉酸浓度的升高或犬尿酸浓度的降低会加重多种疾病的症状。根据大量研究，帕金森病患者的犬尿酸水平降低。同样值得注意的是，在动物实验中，犬尿酸治疗可预防喹啉酸诱导的大鼠纹状体损伤。给予犬尿酸可能是一种有前景的治疗方法，但其应用受到限制，因为它很难透过血脑屏障。解决办法可能是开发犬尿酸类似物（如葡萄糖胺-犬尿酸），其可以透过该屏障并在脑内释放，然后犬尿酸可以通过与兴奋性谷氨酸受体，特别是N-甲基-D-天冬氨酸受体结合发挥其神经保护作用。此外，使用犬尿氨酸衍生物（如4-氯犬尿氨酸）或酶抑制剂（如Ro-61-8048）来确保中枢神经系统中犬尿酸浓度的增加似乎是有希望的。
