These authors contributed equally to this work.
Deleterious effects of neuronal accumulation of glycogen in flies and mice
Article first published online: 2 MAY 2012
Copyright © 2012 EMBO Molecular Medicine
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
EMBO Molecular Medicine
Volume 4, Issue 8, pages 719–729, August 2012
How to Cite
Duran, J., Tevy, M. F., Garcia-Rocha, M., Calbó, J., Milán, M. and Guinovart, J. J. (2012), Deleterious effects of neuronal accumulation of glycogen in flies and mice. EMBO Mol Med, 4: 719–729. doi: 10.1002/emmm.201200241
- Issue published online: 3 AUG 2012
- Article first published online: 2 MAY 2012
- Manuscript Revised: 22 MAR 2012
- Manuscript Accepted: 22 MAR 2012
- Manuscript Received: 9 NOV 2011
- Spanish Ministerio de Ciencia e Innovación. Grant Numbers: BFU2010-21123, CSD2007-00008
- Generalitat de Catalunya. Grant Number: 2005 SGR 00118
- Dirección General de Investigación Científica y Técnica. Grant Number: BFU2008-00769
- Generalitat de Catalunya. Grant Number: 2009 SGR 01176
- glucose metabolism;
- Lafora disease;
Under physiological conditions, most neurons keep glycogen synthase (GS) in an inactive form and do not show detectable levels of glycogen. Nevertheless, aberrant glycogen accumulation in neurons is a hallmark of patients suffering from Lafora disease or other polyglucosan disorders. Although these diseases are associated with mutations in genes involved in glycogen metabolism, the role of glycogen accumulation remains elusive. Here, we generated mouse and fly models expressing an active form of GS to force neuronal accumulation of glycogen. We present evidence that the progressive accumulation of glycogen in mouse and Drosophila neurons leads to neuronal loss, locomotion defects and reduced lifespan. Our results highlight glycogen accumulation in neurons as a direct cause of neurodegeneration.