Identification of novel biomarkers for Parkinson's disease by metabolomic technologies
Identification of novel biomarkers for Parkinson's disease by metabolomic technologies
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DOI：
10.1136/jnnp-2014-309676
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发表时间：
2016-03-01
影响因子：
11
通讯作者：
Hattori, Nobutaka
中科院分区：
文献类型：
--
作者：
Hatano, Taku;Saiki, Shinji;Hattori, Nobutaka
目的 帕金森病（PD）的发病机制涉及环境因素和遗传因素之间的复杂相互作用。代谢组学可以揭示许多疾病（包括神经退行性疾病）中代谢途径的改变。在本研究中，我们试图阐明与帕金森病相关的候选代谢途径。
方法 从35例无痴呆的特发性帕金森病患者和15例年龄匹配的无帕金森病的健康对照参与者中采集血清样本。该分析使用了三个独立平台的组合：针对碱性物质优化的超高效液相色谱/串联质谱（UPLC/MS/MS）、针对酸性物质优化的UPLC/MS/MS以及气相色谱/质谱（GC/MS）。
结果 帕金森病的代谢组学特征与正常对照组明显不同。帕金森病患者的色氨酸、咖啡因及其代谢产物、胆红素和麦角硫因水平显著低于正常对照组，而左旋多巴代谢产物和胆绿素水平则显著高于正常对照组。胆红素/胆绿素比值和麦角硫因的改变可表明氧化应激强度，并可能提示氧化应激升高和/或清除自由基的能力不足，这可能有助于帕金森病的发病机制。血清色氨酸水平降低与帕金森病的精神问题有关。血清咖啡因水平降低与过去流行病学研究中咖啡因摄入与帕金森病发展的负相关一致。
结论 代谢组学分析检测到了与帕金森病发病机制和疾病进展相关的生物标志物。由于需要在帕金森病中确定关键的代谢生物标志物，未来的研究应包括在独立队列中的检测验证和重复。
Objective The pathogenesis of Parkinson's disease (PD) involves complex interactions between environmental and genetic factors. Metabolomics can shed light on alterations in metabolic pathways in many diseases, including neurodegenerative diseases. In the present study, we attempted to elucidate the candidate metabolic pathway(s) associated with PD.Methods Serum samples were collected from 35 individuals with idiopathic PD without dementia and 15 healthy age-matched control participants without PD. This analysis used a combination of three independent platforms: ultrahigh-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) optimised for basic species, UPLC/MS/MS optimised for acidic species and gas chromatography/MS (GC/MS).Results The metabolomic profiles of PD were clearly different from normal controls. PD profiles had significantly lower levels of tryptophan, caffeine and its metabolites, bilirubin and ergothioneine, and significantly higher levels of levodopa metabolites and biliverdin than those of normal controls. Alterations in the bilirubin/biliverdin ratio and ergothioneine can indicate oxidative stress intensity and may suggest elevated oxidative stress and/or insufficient ability for scavenging free radicals, which could contribute to PD pathogenesis. Decreased serum tryptophan level is associated with psychiatric problems in PD. A decrease in serum caffeine levels is consistent with an inverse association of caffeine consumption with development of PD based on past epidemiological studies.Conclusions Metabolomic analysis detected biomarkers associated with PD pathogenesis and disease progression. Since critical metabolic biomarkers need to be identified in PD, future studies should include assay validation and replication in independent cohorts.