NMR Spectroscopy-based Metabolomics of Drosophila Model of Huntington’s Disease Suggests Altered Cell Energetics

Autor: Ashwani Kumar Thakur, Neeraj Sinha, Raj Kumar Sharma, Pradip Sinha, Thamarailingam Athilingam, Virender Singh
Rok vydání: 2017
Předmět:
Zdroj: Journal of Proteome Research. 16:3863-3872
ISSN: 1535-3907
1535-3893
Popis: 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 1H 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, pyruv...
Databáze: OpenAIRE