Related ArticlesNMR 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]
Scientists Observe Structure of Protein That Plays Major Role in Huntington's Disease, Opening Door to Finding Cause ... - Huntington's Disease News
Scientists Observe Structure of Protein That Plays Major Role in Huntington's Disease, Opening Door to Finding Cause ... - Huntington's Disease News
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Huntington's Disease News
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Scientists Observe Structure of Protein That Plays Major Role in Huntington's Disease, Opening Door to Finding Cause ...
Huntington's Disease News
Leibniz-Institut für Molekulare Pharmakologie (FMP) researchers used a combination of nuclear magnetic...
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02-10-2016 09:28 PM
Protein Plaques in Huntington's Patients Have Distinct Structures That Hint at Disease Mechanisms - Huntington's Disease News
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Protein Plaques in Huntington's Patients Have Distinct Structures That Hint at Disease Mechanisms
Huntington's Disease News
Researchers at the University of Pittsburgh School of Medicine used advanced nuclear magnetic resonance spectroscopy to directly assess and characterize huntingtin fibrils and other polyglutamine aggregates. Results showed that, unlike what previous ...
Protein Plaques in Huntington's Patients Have Distinct Structures That Hint at Disease Mechanisms - Huntington's Disease News
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02-06-2016 03:05 AM
Study finding could shed light on molecular mechanisms underlying Huntington's disease - News-Medical.net
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Study finding could shed light on molecular mechanisms underlying Huntington's disease
News-Medical.net
... the process," he said. "Using advanced nuclear magnetic resonance spectroscopy, we were able to provide an unprecedented view of the internal structure of the protein clumps that form in the disease, which we hope will one day lead to new therapies ...
Researchers Describe Brain Plaques Involved In...
[NMR paper] (1)H NMR-Based Metabolite Profiling of Plasma in a Rat Model of Chronic Kidney Disease.
(1)H NMR-Based Metabolite Profiling of Plasma in a Rat Model of Chronic Kidney Disease.
(1)H NMR-Based Metabolite Profiling of Plasma in a Rat Model of Chronic Kidney Disease.
PLoS One. 2014 Jan 20;9(1):e85445
Authors: Kim JA, Choi HJ, Kwon YK, Ryu do H, Kwon TH, Hwang GS
Abstract
Chronic kidney disease (CKD) is characterized by the gradual loss of the kidney function to excrete wastes and fluids from the blood. (1)H NMR-based metabolomics was exploited to investigate the altered metabolic pattern in rats with CKD induced by surgical...
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01-28-2014 11:53 AM
[NMR paper] NMR-based metabolomics of urine in a mouse model of Alzheimer's disease: identification of oxidative stress biomarkers.
NMR-based metabolomics of urine in a mouse model of Alzheimer's disease: identification of oxidative stress biomarkers.
Related Articles NMR-based metabolomics of urine in a mouse model of Alzheimer's disease: identification of oxidative stress biomarkers.
J Clin Biochem Nutr. 2013 Mar;52(2):133-8
Authors: Fukuhara K, Ohno A, Ota Y, Senoo Y, Maekawa K, Okuda H, Kurihara M, Okuno A, Niida S, Saito Y, Takikawa O
Abstract
Alzheimer's disease (AD) is the most common cause of neurodegenerative dementia among elderly patients. A biomarker...
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03-26-2013 01:30 PM
NMR-based metabolomics of mammalian cell and tissue cultures
NMR-based metabolomics of mammalian cell and tissue cultures
Abstract NMR spectroscopy was used to evaluate growth media and the cellular metabolome in two systems of interest to biomedical research. The first of these was a Chinese hamster ovary cell line engineered to express a recombinant protein. Here, NMR spectroscopy and a quantum mechanical total line shape analysis were utilized to quantify 30 metabolites such as amino acids, Krebs cycle intermediates, activated sugars, cofactors, and others in both media and cell extracts. The impact of bioreactor scale and addition of...
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03-09-2011 04:19 AM
NMR-based metabolomics of mammalian cell and tissue cultures.
NMR-based metabolomics of mammalian cell and tissue cultures.
NMR-based metabolomics of mammalian cell and tissue cultures.
J Biomol NMR. 2011 Mar 4;
Authors: Aranibar N, Borys M, Mackin NA, Ly V, Abu-Absi N, Abu-Absi S, Niemitz M, Schilling B, Li ZJ, Brock B, Russell RJ, Tymiak A, Reily MD
NMR spectroscopy was used to evaluate growth media and the cellular metabolome in two systems of interest to biomedical research. The first of these was a Chinese hamster ovary cell line engineered to express a recombinant protein. Here, NMR spectroscopy and a...