Journal
JOURNAL OF PROTEOME RESEARCH
Volume 14, Issue 1, Pages 467-478Publisher
AMER CHEMICAL SOC
DOI: 10.1021/pr500807t
Keywords
metabolite signature; idiopathic Parkinson's disease; urinary metabolomics; metabolic phenotype; drosophila
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Funding
- Food and Health Bureau of Hong Kong Government [HHSRF08091111]
- PuraPharm International (H.K.), Ltd.
- Interdisciplinary Research Match Scheme Grants from Hong Kong Baptist University [IRMS/12-13/1A]
- Dr. Ho Tzu-leung's Foundation
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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.
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