Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary.
J Neurol Sci. 2011 Nov 15;310(1-2):256-60. doi: 10.1016/j.jns.2011.07.021. Epub 2011 Aug 6.
Parkinson's disease (PD) is one of the most common disabling neurodegenerative diseases. Although several therapeutic approaches are available, there are two major unresolved issues: the lack of proved neuroprotective therapy and the treatment of L-dopa-induced motor complications. In the brain, 90% of the tryptophan is metabolized in the kynurenine pathway. Some of the intermediates, such as quinolinic acid and 3-hydroxy kynurenine, are neurotoxic, while others, such as kynurenic acid, are putative intrinsic neuroprotective compounds, mainly by acting as endogenous antagonists of ionotropic excitatory amino acid receptors. Alterations in the kynurenine pathway have been demonstrated in PD. Preclinical data suggest that intervention in the kynurenine pathway may result in neuroprotection and may alleviate L-dopa-induced dyskinesia. There are two alternative approaches for such intervention: the use of kynurenic acid analogues or pro-drugs, or modulation of the activities of the intrinsic enzymes of the pathway.
帕金森病（PD）是最常见的致残神经退行性疾病之一。尽管有几种治疗方法可用，但仍存在两个主要未解决的问题：缺乏经过证实的神经保护疗法和治疗 L-多巴诱导的运动并发症。在大脑中，90%的色氨酸在犬尿氨酸途径中代谢。一些中间产物，如喹啉酸和 3-羟基犬尿氨酸，具有神经毒性，而另一些中间产物，如犬尿氨酸，是潜在的内源性神经保护化合物，主要通过作为离子型兴奋性氨基酸受体的内源性拮抗剂发挥作用。在 PD 中已经证明了犬尿氨酸途径的改变。临床前数据表明，干预犬尿氨酸途径可能导致神经保护，并可能减轻 L-多巴诱导的运动障碍。有两种替代方法可以进行这种干预：使用犬尿氨酸类似物或前药，或调节途径中内源性酶的活性。
