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Targeted biochemical profiling of brain from Huntington's disease patients reveals novel metabolic pathways of interest
- Source :
- Graham, S F, Pan, X, Yilmaz, A, Macias, S, Robinson, A, Mann, D & Green, B D 2018, ' Targeted biochemical profiling of brain from Huntington's disease patients reveals novel metabolic pathways of interest ', Biochimica et biophysica acta, vol. 1864, no. 7, pp. 2430-2437 . https://doi.org/10.1016/j.bbadis.2018.04.012
- Publication Year :
- 2018
-
Abstract
- Huntington's disease (HD) is a devastating, progressive neurodegenerative disease with a distinct phenotype characterized by chorea and dystonia, incoordination, cognitive decline and behavioral difficulties. The precise mechanisms of HD progression are poorly understood; however, it is known that there is an expansion of the trinucleotide cytosine-adenine-guanine (CAG) repeat in the Huntingtin gene. Herein DI/LC-MS/MS was used to accurately identify and quantify 185 metabolites in post mortem frontal lobe and striatum from HD patients and healthy control cases. The findings link changes in energy metabolism and phospholipid metabolism to HD pathology and also demonstrate significant reductions in neurotransmitters. Further investigation into the oxidation of fatty acids and phospholipid metabolism in pre-clinical models of HD are clearly warranted for the identification of potential therapies. Additionally, panels of 5 metabolite biomarkers were identified in both the frontal lobe (AUC = 0.962 (95% CI: 0.85–1.00) and striatum (AUC = 0.988 (95% CI: 0.899–1.00). This could have clinical utility in more accessible biomatrices such as blood serum for the early detection of those entering the prodromal phase of the disease, when treatment is believed to be most effective. Further evaluation of these biomarker panels in human cohorts is justified to determine their clinical efficacy.
- Subjects :
- 0301 basic medicine
Male
Disease
Bioinformatics
03 medical and health sciences
0302 clinical medicine
Blood serum
Huntington's disease
medicine
Journal Article
Humans
Cognitive decline
Molecular Biology
Aged
Dystonia
Aged, 80 and over
business.industry
Chorea
Middle Aged
medicine.disease
Corpus Striatum
Frontal Lobe
030104 developmental biology
Huntington Disease
Frontal lobe
Molecular Medicine
Biomarker (medicine)
Female
medicine.symptom
business
030217 neurology & neurosurgery
Biomarkers
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Graham, S F, Pan, X, Yilmaz, A, Macias, S, Robinson, A, Mann, D & Green, B D 2018, ' Targeted biochemical profiling of brain from Huntington's disease patients reveals novel metabolic pathways of interest ', Biochimica et biophysica acta, vol. 1864, no. 7, pp. 2430-2437 . https://doi.org/10.1016/j.bbadis.2018.04.012
- Accession number :
- edsair.doi.dedup.....3bb956c64f8f204d03eed721f1577c24