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The metabolomics of alpha-synuclein (SNCA) gene deletion and mutation in mouse brain

Citation

Musgrove, RE and Horne, H and Wilson, R and King, AE and Edwards, LM and Dickson, TC, The metabolomics of alpha-synuclein (SNCA) gene deletion and mutation in mouse brain, Metabolomics, 10, (1) pp. 114-122. ISSN 1573-3882 (2014) [Refereed Article]

Copyright Statement

Copyright 2013 Springer Science+Business Media New York

DOI: doi:10.1007/s11306-013-0561-6

Abstract

Using a novel metabolomics approach the current study aimed to further characterize the functional attributes of alpha-synuclein that mediate its involvement in neurodegeneration. The metabolic profiles of alpha-synuclein knockout and A53T mutant overexpressing mouse brains were studied using proton nuclear magnetic resonance (1H NMR) and liquid chromatography mass spectrometry (LC/MS). Gene deletion and mutation were both associated with significant alterations in brain energy metabolism when compared with their respective wild-type controls. These changes indicated deficiencies in key metabolic pathways, including the tricarboxylic acid cycle, and significant differences in the concentrations of small molecules including adenine nucleotides, taurine, NAD+ and glutamine. Analysis of the metabolic pathways affected by both knockout and mutation further indicated involvement of alpha-synuclein in metabolic pathways of energy metabolism, cellular redox status and glycerophospholipid metabolism. As such, our data identify novel functions of alpha-synuclein, validate previous reports describing its contribution to energy metabolism and lipid synthesis and support the use of metabolomic analysis as a fundamental technique in defining the effect of protein expression and mutation in genetic models.

Item Details

Item Type:Refereed Article
Keywords:alpha-synuclein, brain, metabolomics, Parkinsonís disease, proton nuclear magnetic resonance (1H NMR), liquid chromatography mass spectrometry (LC/MS)
Research Division:Biological Sciences
Research Group:Biochemistry and Cell Biology
Research Field:Cell Metabolism
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Neurodegenerative Disorders Related to Ageing
Author:Musgrove, RE (Ms Ruth Musgrove)
Author:Horne, H (Dr James Horne)
Author:Wilson, R (Dr Richard Wilson)
Author:King, AE (Associate Professor Anna King)
Author:Edwards, LM (Dr Lindsay Edwards)
Author:Dickson, TC (Associate Professor Tracey Dickson)
ID Code:85351
Year Published:2014
Web of Science® Times Cited:4
Deposited By:Central Science Laboratory
Deposited On:2013-07-01
Last Modified:2017-11-06
Downloads:0

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