Open AccessMetabolomics‐based identification of metabolic alterations in PARK2
Author(s) -
Okuzumi Ayami,
Hatano Taku,
Ueno ShinIchi,
Ogawa Takashi,
Saiki Shinji,
Mori Akio,
Koinuma Takahiro,
Oji Yutaka,
Ishikawa KeiIchi,
Fujimaki Motoki,
Sato Shigeto,
Ramamoorthy Sivapriya,
Mohney Robert P.,
Hattori Nobutaka
Publication year - 2019
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.724
Subject(s) - metabolomics , parkin , medicine , metabolic pathway , metabolite , compound heterozygosity , metabolism , endocrinology , case control study , metabolome , biochemistry , disease , biology , bioinformatics , phenotype , parkinson's disease , gene
Objective Parkin is the causative gene for autosomal recessive familial Parkinson's disease ( PD ), although it remains unclear how parkin dysfunction is involved with the general condition. Recently, serum and/or plasma metabolomics revealed alterations in metabolic pathways that might reflect pathomechanisms of idiopathic PD ( iPD ). Thus, we hypothesized that serum metabolomics of patients with homozygous or compound heterozygous parkin mutations (namely, PARK 2) might reflect metabolic alterations due to parkin dysfunction. Methods We enrolled 15 PARK 2 patients (52 ± 17.6 years) confirmed with homozygous (seven cases) and compound heterozygous (eight cases) parkin mutations, along with 19 healthy age‐matched controls (51 ± 11.5 years). We analyzed 830 metabolites from participants’ serum using well‐established metabolomics technologies, including ultra‐high performance liquid chromatography/tandem mass spectroscopy. Results Based on metabolic profiles, hierarchical matrix analysis can divide samples between control and PARK 2 subjects. Profiles from PARK 2 patients showed significantly higher levels of fatty acid ( FA ) metabolites and oxidized lipids, and significantly lower levels of antioxidant, caffeine, and benzoate‐related metabolites. Interpretation Metabolomics can identify specific metabolic alterations in PARK 2 patients compared with controls. Alterations in FA metabolites suggest a relationship between parkin function and lipid metabolism. The elevation of oxidized lipids in combination with decreasing antioxidants may reflect general hyperoxidative stress. Decreasing benzoate‐related metabolites might be due to the alteration in gut microbiota. Consequently, caffeine and its metabolites may be decreased due to malabsorption. These findings are similar to metabolic alterations in iPD . Thus, serum/plasma metabolomics may reflect the association between parkin dysfunction and parkinsonism.