Beal M F, Matson W R, Swartz K J, Gamache P H, Bird E D
Department of Neurology, Massachusetts General Hospital, Boston 02114.
J Neurochem. 1990 Oct;55(4):1327-39. doi: 10.1111/j.1471-4159.1990.tb03143.x.
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 less than 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 neurotransmission and can block excitotoxic degeneration in vivo, a relative deficiency of this compound could directly contribute to neuronal degeneration in HD.
最近的证据表明，在亨廷顿舞蹈病（HD）中，兴奋性氨基酸受体的N-甲基-D-天冬氨酸（NMDA）亚型可能存在过度激活。色氨酸通过犬尿氨酸途径代谢，产生NMDA受体激动剂喹啉酸和NMDA受体拮抗剂犬尿喹啉酸。在本研究中，采用具有16传感器电化学检测的高效液相色谱法，对35名对照者和30名HD患者死后壳核中酪氨酸和色氨酸代谢途径的多个成分进行了定量分析。与先前关于HD壳核的报道一致，5-羟吲哚乙酸、5-羟色氨酸和血清素浓度显著增加。在犬尿氨酸途径中，与对照组相比，HD患者中犬尿氨酸与犬尿喹啉酸的比率显著（p小于0.01）增加了两倍，这与HD中犬尿喹啉酸生成减少一致。与对照组和其他神经系统疾病患者相比，HD患者脑脊液中犬尿喹啉酸的浓度显著降低。由于犬尿喹啉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，这种化合物的相对缺乏可能直接导致HD中的神经元变性。
