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

journal contribution
posted on 2023-05-17, 18:36 authored by Ruth MusgroveRuth Musgrove, Henry HorneHenry Horne, Richard WilsonRichard Wilson, Anna KingAnna King, Edwards, LM, Tracey DicksonTracey Dickson
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.

History

Publication title

Metabolomics

Volume

10

Pagination

114-122

ISSN

1573-3882

Department/School

Menzies Institute for Medical Research

Publisher

Springer Verlag

Place of publication

NEW YORK, NY 10013 USA

Rights statement

Copyright 2013 Springer Science+Business Media New York

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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