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Deleterious effects of neuronal accumulation of glycogen in flies and mice

  1. Jordi Duran1,2,†,
  2. María Florencia Tevy1,2,†,
  3. Mar Garcia-Rocha1,2,
  4. Joaquim Calbó1,2,
  5. Marco Milán1,3,*,
  6. Joan J. Guinovart1,2,4,*

Article first published online: 2 MAY 2012

DOI: 10.1002/emmm.201200241

Issue

EMBO Molecular Medicine

EMBO Molecular Medicine

Volume 4, Issue 8, pages 719–729, August 2012

Additional Information

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

Author Information

  1. 1

    Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain

  2. 2

    Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain

  3. 3

    Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain

  4. 4

    Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain

  1. †

    These authors contributed equally to this work.

*Tel: + 34 93 4034902; Fax: + 34 93 4037109

  • †

    These authors contributed equally to this work.

Publication History

  1. Issue published online: 3 AUG 2012
  2. Article first published online: 2 MAY 2012
  3. Manuscript Revised: 22 MAR 2012
  4. Manuscript Accepted: 22 MAR 2012
  5. Manuscript Received: 9 NOV 2011

Funded by

  • 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

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Keywords:

  • Drosophila;
  • glucose metabolism;
  • glycogen;
  • Lafora disease;
  • neurodegeneration

Abstract

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.

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