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Impaired PLP-dependent metabolism in brain samples from Huntington disease patients and transgenic R6/1 mice.
- Source :
-
Metabolic brain disease [Metab Brain Dis] 2016 Jun; Vol. 31 (3), pp. 579-86. Date of Electronic Publication: 2015 Dec 14. - Publication Year :
- 2016
-
Abstract
- Oxidative stress has been described as important to Huntington disease (HD) progression. In a previous HD study, we identified several carbonylated proteins, including pyridoxal kinase and antiquitin, both of which are involved in the metabolism of pyridoxal 5´-phosphate (PLP), the active form of vitamin B6. In the present study, pyridoxal kinase levels were quantified and showed to be decreased both in HD patients and a R6/1 mouse model, compared to control samples. A metabolomic analysis was used to analyze metabolites in brain samples of HD patients and R6/1 mice, compared to control samples using mass spectrometry. This technique allowed detection of increased concentrations of pyridoxal, the substrate of pyridoxal kinase. In addition, PLP, the product of the reaction, was decreased in striatum from R6/1 mice. Furthermore, glutamate and cystathionine, both substrates of PLP-dependent enzymes were increased in HD. This reinforces the hypothesis that PLP synthesis is impaired, and could explain some alterations observed in the disease. Together, these results identify PLP as a potential therapeutic agent.
- Subjects :
- Adult
Aged
Animals
Cystathionine metabolism
Disease Models, Animal
Disease Progression
Female
Glutamic Acid metabolism
Humans
Male
Mice
Mice, Transgenic
Middle Aged
Young Adult
Cerebral Cortex metabolism
Corpus Striatum metabolism
Huntington Disease metabolism
Oxidative Stress physiology
Pyridoxal Phosphate metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1573-7365
- Volume :
- 31
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Metabolic brain disease
- Publication Type :
- Academic Journal
- Accession number :
- 26666246
- Full Text :
- https://doi.org/10.1007/s11011-015-9777-7