| Autor: |
Pears MR; Department of Biochemistry, University of Cambridge, Hopkins Building, Tennis Court Road, Cambridge CB21QW, UK., Codlin S, Haines RL, White IJ, Mortishire-Smith RJ, Mole SE, Griffin JL |
| Jazyk: |
angličtina |
| Zdroj: |
Molecular bioSystems [Mol Biosyst] 2010 Jun; Vol. 6 (6), pp. 1093-102. Date of Electronic Publication: 2010 Mar 17. |
| DOI: |
10.1039/b915670d |
| Abstrakt: |
The neuronal ceroid lipofuscinoses (NCLs) constitute a group of autosomal recessive neurodegenerative diseases affecting children. To date, the disease pathogenesis remains unknown, although the role of lysosomal impairment is widely recognized across the different diseases. Recently, the creation of simple models of juvenile NCL (Batten disease) has provided additional insights into the disease mechanism at the molecular level. We report defects in metabolism identified in the Schizosacchromyces pombe yeast model, where btn1, the orthologue of CLN3, has been deleted, using a metabolomics approach based on high resolution 1H and 13C NMR spectroscopy. Such changes represent the first documented metabolic changes associated with deletion of btn1. A decrease in extracellular glucose and increases in the concentration of extracellular ethanol and alanine labelling demonstrate increased glycolytic flux that may arise from vacuolar impairment, whilst amino acid changes were detected which were also in accordance with defective vacuolar functionality. That these changes were detected using a metabolomic based approach advocates its use to further analyse other yeast models of human disease to better understand the function of orthologue genes. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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