Faculty of Biomedical & Life Sciences, Neuroscience and Molecular Pharmacology, University of Glasgow, Glasgow, UK.
J Neurochem. 2010 Jan;112(1):112-22. doi: 10.1111/j.1471-4159.2009.06442.x. Epub 2009 Oct 20.
There is substantial evidence that abnormal concentrations of oxidised tryptophan metabolites, produced via the kynurenine pathway, contribute to progressive neurodegeneration in Huntington's disease. We have now examined the blood levels of these metabolites in patients at different stages of Huntington's disease, assessed both in terms of clinical disease severity and numbers of CAG repeats. Close relatives of the patients were included in the study as well as unrelated healthy controls. Levels of lipid peroxidation products, the pro-inflammatory cytokine interleukin (IL)-23 and the soluble human leucocyte antigen-G (sHLA-G) were also measured. There were lower levels of tryptophan and a higher kynurenine : tryptophan ratio, indicating activation of indoleamine-2,3-dioxygenase, in the most severely affected group of patients, with increased levels of IL-23 and sHLA-G. Marked correlations were noted between IL-23 and the patient severity group, anthranilic acid levels and the number of CAG repeats, and between anthranilic acid and IL-23, supporting our previous evidence of a relationship between anthranilic acid and inflammatory status. Tryptophan was negatively correlated with symptom severity and number of CAG repeats, and positively correlated with sHLA-G. The results support the proposal that tryptophan metabolism along the kynurenine pathway in Huntington's disease is related to the degree of genetic abnormality, to clinical disease severity and to aspects of immunopathogenesis.
有大量证据表明，犬尿氨酸途径产生的氧化色氨酸代谢物浓度异常，导致亨廷顿病的进行性神经退行性变。我们现在已经检查了处于亨廷顿病不同阶段的患者的这些代谢物的血液水平，既根据临床疾病严重程度，也根据 CAG 重复次数进行了评估。该研究还包括了患者的近亲以及无关的健康对照者。还测量了脂质过氧化产物、促炎细胞因子白细胞介素 (IL)-23 和可溶性人类白细胞抗原-G (sHLA-G) 的水平。在病情最严重的患者组中，色氨酸水平较低，犬尿氨酸与色氨酸的比值较高，表明吲哚胺 2,3-双加氧酶被激活，IL-23 和 sHLA-G 水平升高。IL-23 与患者严重程度组、邻氨基苯甲酸水平和 CAG 重复次数之间，以及邻氨基苯甲酸与 IL-23 之间存在显著相关性，支持我们之前关于邻氨基苯甲酸与炎症状态之间存在关系的证据。色氨酸与症状严重程度和 CAG 重复次数呈负相关，与 sHLA-G 呈正相关。研究结果支持这样的假设，即亨廷顿病中犬尿氨酸途径的色氨酸代谢与遗传异常程度、临床疾病严重程度以及免疫发病机制的某些方面有关。
