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

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 (H 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. [ABSTRACT FROM AUTHOR]