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J Nutr Biochem. 2016 May;31:38-44. doi: 10.1016/j.jnutbio.2015.12.001. Epub 2016 Jan 4.

Metabolic disturbances in plasma as biomarkers for Huntington's disease.

Author information

1
Healthy Aging Research Center, Chang Gung University, Tao-Yuan, Taiwan; Metabolomics Core Laboratory, Chang Gung University, Tao-Yuan, Taiwan; Department of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
2
Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang-Gung University, Tao-Yuan, Taiwan.
3
Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang-Gung University, Tao-Yuan, Taiwan. Electronic address: cmchen@adm.cgmh.org.tw.

Abstract

Huntington's disease (HD), caused by expanded CAG repeats encoding a polyglutamine tract in the huntingtin protein, presents with a predominant degeneration of neurons in the striatum and cortex. Although a few studies have identified substantial metabolite alterations in plasma, the picture of plasma metabolomics of HD has not been clearly depicted yet. Using a global metabolomics screening for plasma from 15 HD patients and 17 controls, HD patient group was separated from the control group by a panel of metabolites belonging to carnitine, amino acid and phosphatidylcholine species. The quantification of 184 related metabolites (including carnitine, amino acid and phosphatidylcholine species) in 29 HD patients, 9 presymptomatic HD carriers and 44 controls further showed one up-regulated (glycine) and 9 down-regulated metabolites (taurine, serotonin, valine, isoleucine, phosphatidylcholine acyl-alkyl C36:0 and C34:0 and lysophosphatidylcholine acyl C20:3). To understand the biosynthetic alterations of phosphatidylcholine in HD, we examined the expression levels and activities of a panel of key enzymes responsible for phosphatidylcholine metabolism. The results showed down-regulation of PCYT1A and increased activity of phospholipase A2 in HD leukocytes. These metabolic profiles strongly indicate that disturbed metabolism is involved in pathogenesis of HD and provide clue for the development of novel treatment strategies for HD.

KEYWORDS:

Amino acid; Biomarkers; Huntington's disease; Metabolomics; PCYT1A; Phosphatidylcholine; Phospholipase A(2)

PMID:
27133422
DOI:
10.1016/j.jnutbio.2015.12.001
[Indexed for MEDLINE]

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