LC MS-Based Urinary Metabolite Signatures in Idiopathic Parkinson's Disease
LC MS-Based Urinary Metabolite Signatures in Idiopathic Parkinson's Disease
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DOI：
10.1021/pr500807t
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发表时间：
2015-01-01
影响因子：
4.4
通讯作者：
Cai, Zongwei
中科院分区：
文献类型：
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作者：
Luan, Hemi;Liu, Liang-Feng;Cai, Zongwei
越来越多的证据表明，体液中的异常代谢表型反映了帕金森病（PD）的发病机制和病理生理学。这些体液包括尿液;然而，具体而言，尿代谢表型与PD之间的关系尚未完全了解。在这项研究中，尿代谢产物从共401个临床尿液样本收集自106特发性PD患者和104正常对照组进行了分析，通过使用高效液相色谱-高分辨率质谱联用。我们的研究揭示了临床表型和尿代谢产物谱之间的显着相关性。特发性PD患者的代谢特征与正常对照组显著且一致地不同，在类固醇生成、脂肪酸β-氧化、组氨酸代谢、苯丙氨酸代谢、色氨酸代谢、核苷酸代谢和酪氨酸代谢中观察到相关代谢途径变异。在果蝇黑腹果蝇中，色氨酸代谢中犬尿氨酸途径的改变与α-突触核蛋白过表达的果蝇PD模型中的致病变化相对应。结果表明，基于LC-MS的尿液代谢组学分析可以揭示代谢物特征和代谢途径中表征PD的相关变化。跨物种的一致的PD相关变化可能为在分子水平上理解PD的代谢调节提供基础。
Increasing evidence has shown that abnormal metabolic phenotypes in body fluids reflect the pathogenesis and pathophysiology of Parkinson's disease (PD). These body fluids include urine; however, the relationship between, specifically, urinary metabolic phenotypes and PD is not fully understood. In this study, urinary metabolites from a total of 401 clinical urine samples collected from 106 idiopathic PD patients and 104 normal control subjects were profiled by using high-performance liquid chromatography coupled to high-resolution mass spectrometry. Our study revealed significant correlation between clinical phenotype and urinary metabolite profile. Metabolic profiles of idiopathic PD patients differed significantly and consistently from normal controls, with related metabolic pathway variations observed in steroidogenesis, fatty acid beta-oxidation, histidine metabolism, phenylalanine metabolism, tryptophan metabolism, nucleotide metabolism, and tyrosine metabolism. In the fruit fly Drosophila melanogaster, the alteration of the kynurenine pathway in tryptophan metabolism corresponded with pathogenic changes in the alpha-synuclein overexpressed Drosophila model of PD. The results suggest that LC-MS-based urinary metabolomic profiling can reveal the metabolite signatures and related variations in metabolic pathways that characterize PD. Consistent PD-related changes across species may provide the basis for understanding metabolic regulation of PD at the molecular level.