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B35 Glutamine synthetase-1 induces autophagy and neuronal survival in a drosophila model huntington’s disease
  1. Maria Enrica Pasini1,
  2. Chiara Paiardi1,
  3. Luisa Vernizzi1,
  4. Alice Valenza1,
  5. Giusimaria Licata1,
  6. Teresa Vitali1,2,3,
  7. Maria Antonietta Vanoni1,
  8. Cinzia Gellera2,
  9. Manuela Rizzetto2,
  10. Franco Taroni2,
  11. Caterina Mariotti2,
  12. Paola Bellosta1
  1. 1University of Milan, Milan, Italy
  2. 2Carlo Besta Neurological Institute, Milan, Italy
  3. 3NIH/NCI Centre for Cancer Research, Bethesda, Maryland, USA

Abstract

Background Neuronal death is often caused by an excess of glutamate that is maintained at physiological level by a non-autonomous cycle between glia and neurons called the glutamate-glutamine cycle.

Aims It is possible to manipulate the activity of the enzymes that regulate the glutamate-glutamine cycle to ameliorate neuronal death? To answer this question we are taking advantage of Drosophila models used to dissect the cellular and molecular events of neurodegenerative disorders. Glutamate removal from the synaptic cleft by neuroglia is reduced in mouse models of Huntington’s disease (HD) and in HD patients.

Results Our genetic and biochemical data suggest a key function for the enzyme Glutamine Synthetase-1 in ameliorating animal motility and neuronal loss in a Drosophila model for HD by inducing autophagy, a physiological process necessary to keep the neurons healthy by cleaning them from cellular debris and Huntingtin-protein aggregates.

Methods We are using genetic and biochemical assays to understand how the metabolic components of the glutamate and glutamine catabolism, which are regulated by the activity of the enzymes Glutamine Synthetase, Glutamine Dehydrogenase and Glutaminase, affects autophagy in neuronal and glial cells, in normal and pathological conditions. In addition, we are preforming feeding experiments to understand if the assimilation of glutamine and glutamate might affect the viability and survival of the animals using a Drosophila model for HD.

Conclusions Our preliminary results show that glutamine in the food increases animal life-span, both in wild-type and HD animals, while glutamate has the opposite effect.

  • Glutamate
  • Glutamine
  • Huntingtin
  • Autophagy
  • Drosophila
  • Neuron
  • Glia

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