KYNURENINE PATHWAY MEASUREMENTS IN HUNTINGTONS-DISEASE STRIATUM - EVIDENCE FOR REDUCED FORMATION OF KYNURENIC ACID
KYNURENINE PATHWAY MEASUREMENTS IN HUNTINGTONS-DISEASE STRIATUM - EVIDENCE FOR REDUCED FORMATION OF KYNURENIC ACID
复制标题
DOI：
10.1111/j.1471-4159.1990.tb03143.x
复制
发表时间：
1990-10-01
影响因子：
4.7
通讯作者：
BIRD, ED
中科院分区：
文献类型：
--
作者：
BEAL, MF;MATSON, WR;BIRD, ED
最近的证据表明，在亨廷顿病（HD）中可能存在兴奋性氨基酸受体的N-甲基-D-天冬氨酸（NMDA）亚型的过度激活。通过犬尿氨酸途径的色氨酸代谢产生喹啉酸（一种NMDA受体激动剂）和犬尿烯酸（一种NMDA受体拮抗剂）。在本研究中，酪氨酸和色氨酸代谢途径的多个组件进行了定量，在35个对照组和30个HD患者的死后壳核，使用HPLC与16传感器电化学检测。与HD壳核中的既往报告一致，5-羟基吲哚乙酸、5-羟基色氨酸和5-羟色胺浓度显著升高。在犬尿氨酸途径内，与对照相比，HD患者中犬尿氨酸与犬尿烯酸的比率显著（p < 0.01）增加两倍，这与HD中犬尿烯酸形成减少一致。与对照组和其他神经系统疾病患者相比，HD患者的CSF犬尿烯酸浓度显著降低。由于犬尿烯酸是兴奋性神经传递的内源性抑制剂，并且可以在体内阻断兴奋性毒性变性，因此该化合物的相对缺乏可能直接导致HD中的神经元变性。
Recent evidence suggests that there may be overactivation of the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptors in Huntington''s disease (HD). Tryptophan metabolism by the kynurenine pathway produces both quinolinic acid, an NMDA receptor agonist, and kynurenic acid, an NMDA receptor antagonist. In the present study, multiple components of the tyrosine and tryptophan metabolic pathways were quantified in postmortem putamen of 35 control and 30 HD patients, using HPLC with 16-sensor electrochemical detection. Consistent with previous reports in HD putamen, there were significant increases in 5-hydroxyindoleacetic acid, 5-hydroxytryptophan, and serotonin concentrations. Within the kynurenine pathway, the ratio of kynurenine to kynurenic acid was significantly (p < 0.01) increased twofold in HD patients as compared with controls, consistent with reduced formation of kynurenic acid in HD. CSF concentrations of kynurenic acid were significantly reduced in HD patients as compared with controls and patients with other neurologic diseases. Because kynurenic acid is an endogenous inhibitor of excitatory neuro transmission and can block excitotoxic degeneration in vivo, a relative deficiency of this compound could directly contribute to neuronal degeneration in HD.