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<\/p>\nThe viability of neurons in the brain depends on a complex series of interconnected biochemical reactions that constitute cellular metabolism. Disruption of these metabolic pathways is associated with neurological conditions, including Alzheimer\u2019s and Parkinson\u2019s. Recent technical advances in the analysis of cellular metabolites mean it is now possible to simultaneously quantify the levels and turnover of multiple metabolites in cells. We are using this technology to compare the metabolite profiles of control cells and cells that lack the protein sacsin, which is mutated in ARSACS. We believe disruption of cellular metabolism is likely to be particularly relevant to ARSACS. This is because it has previously been shown that the health of mitochondria, organelles where key metabolic enzymes are located, is reduced in cellular and animal models of ARSACS. Our goal is to define the metabolic changes that occur in sacsin deficient cells as we believe this will elucidate ARSACS disease mechanism and potentially identify targets for therapeutic intervention. Through this research we have identified disturbance in glutamate-glutamine metabolism in cells lacking sacsin. Glutamate is made from glutamine and these metabolites are important for brain function as glutamate can act as a neurotransmitter, carrying messages between neurons. Thus, a key current objective for the work is to mechanistically understand why glutamate-glutamine metabolism is altered and whether this is relevant for ARSACS.<\/p>\n
Financement : \u00a337,714<\/p>\n
Dur\u00e9e :\u00a0 2i\u00e8me ann\u00e9e d’un projet de 2 ans<\/p>\n
Coordonn\u00e9es:<\/p>\n
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Dr. Paul Chapple, Faculty of Medicine and Dentistry
Queen Mary University of London<\/p>\n
1st Floor North ,John Vane Science Building, Charterhouse Square
London, EC1M 6BQ<\/p>\n