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Default NMR spectroscopy-based metabolomics of Drosophila model of Huntington's disease suggests altered cell energetics.

NMR spectroscopy-based metabolomics of Drosophila model of Huntington's disease suggests altered cell energetics.

Related Articles NMR spectroscopy-based metabolomics of Drosophila model of Huntington's disease suggests altered cell energetics.

J Proteome Res. 2017 Sep 05;:

Authors: Singh V, Sharma RK, Athilingam T, Sinha P, Sinha N, Thakur AK

Abstract
Huntington's disease (HD) is a neurodegenerative disorder induced by aggregation of the pathological form of Huntingtin protein that has expanded polyglutamine (polyQ) repeats. In the Drosophila model, for instance, expression of transgenes with polyQ repeats induce HD-like pathologies progressively correlating with the increasing lengths of these repeats. Previous studies on both animal models and clinical samples have revealed metabolite imbalances during HD progression. To further explore the physiological processes linked to metabolite imbalances during HD, we have investigated 1D (1)H NMR spectroscopy-based metabolomics profile of Drosophila HD model. Using multivariate analysis (PCA and PLS-DA) of metabolites obtained from methanolic extracts of fly heads displaying retinal deformations due to polyQ overexpression, we show that the metabolite imbalance during HD are likely to affect cell energetics. Six out of the 35 metabolites analyzed, namely, nicotinamide adenine dinucleotide (NAD), lactate, pyruvate, succinate, sarcosine, and acetoin displayed segregation with progressive severity of HD. Specifically, HD progression was seen associated with reduction in NAD and increase in lactate-to-pyruvate ratio. Further, comparative analysis of fly HD metabolome with those of mouse HD model, and HD human patients, revealed comparable metabolite imbalances suggesting altered cellular energy homeostasis. These findings thus raise the possibility of therapeutic interventions for HD via modulation of cellular energetics.


PMID: 28871787 [PubMed - as supplied by publisher]



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