Deleterious effects of neuronal accumulation of glycogen in flies and mice

Authors

  • Jordi Duran,

    1. Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain
    2. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain
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    • These authors contributed equally to this work.

  • María Florencia Tevy,

    1. Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain
    2. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain
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    • These authors contributed equally to this work.

  • Mar Garcia-Rocha,

    1. Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain
    2. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain
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  • Joaquim Calbó,

    1. Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain
    2. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain
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  • Marco Milán,

    Corresponding author
    1. Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain
    2. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
    • Marco Milán, Tel: + 34 93 4034902; Fax: + 34 93 4037109

      Joan J. Guinovart, Tel: +34 93 4037111; Fax + 34 93 4037114

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  • Joan J. Guinovart

    Corresponding author
    1. Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain
    2. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain
    3. Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain
    • Marco Milán, Tel: + 34 93 4034902; Fax: + 34 93 4037109

      Joan J. Guinovart, Tel: +34 93 4037111; Fax + 34 93 4037114

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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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