Probing the metabolic aberrations underlying mutant huntingtin toxicity in yeast and assessing their degree of preservation in humans and mice.

Metabolomics is a powerful multiparameter tool for evaluating phenotypic traits associated with disease processes. We have used (1)H NMR metabolome profiling to characterize metabolic aberrations in a yeast model of Huntington's disease that are attributable to the mutant huntingtin protein's gain-of-toxic-function effects. A group of 11 metabolites (alanine, acetate, galactose, glutamine, glycerol, histidine, proline, succinate, threonine, trehalose, and valine) exhibited significant concentration changes in yeast expressing the N-terminal fragment of a mutant human huntingtin gene.