LC鈥揗S-Based Urinary Metabolite Signatures in Idiopathic Parkinson鈥檚 Disease

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• 作者：Hemi Luan ; Liang-Feng Liu ; Nan Meng ; Zhi Tang ; Ka-Kit Chua ; Lei-Lei Chen ; Ju-Xian Song ; Vincent C. T. Mok ; Li-Xia Xie ; Min Li ; Zongwei Cai
• 刊名：Journal of Proteome Research
• 出版年：2015
• 出版时间：January 2, 2015
• 年：2015
• 卷：14
• 期：1
• 页码：467-478
• 全文大小：618K
• ISSN：1535-3907

文摘

Increasing evidence has shown that abnormal metabolic phenotypes in body fluids reflect the pathogenesis and pathophysiology of Parkinson鈥檚 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鈥揗S-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.