LC-MS-based urinary metabolite signatures in idiopathic Parkinson's disease

Hemi Luan, Liangfeng LIU, Nan Meng, Zhi Tang, Ka Kit CHUA, Lei Lei Chen, Juxian SONG, Vincent C.T. Mok, Li Xia Xie, Min LI*, Zongwei CAI

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)467-478
Number of pages12
JournalJournal of Proteome Research
Volume14
Issue number1
DOIs
Publication statusPublished - 2 Jan 2015

Scopus Subject Areas

  • Biochemistry
  • Chemistry(all)

User-Defined Keywords

  • drosophila
  • idiopathic Parkinson's disease
  • metabolic phenotype
  • metabolite signatures
  • urinary metabolomics

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