PTG depletion removes lafora bodies and rescues the fatal epilepsy of lafora disease

Julie Turnbull, Anna A. DePaoli-Roach, Xiaochu Zhao, Miguel A. Cortez, Nela Pencea, Erica Tiberia, Mark Piliguian, Peter J. Roach, Peixiang Wang, Cameron A. Ackerley, Berge A. Minassian

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66 Scopus citations

Abstract

Lafora disease is the most common teenage-onset neurodegenerative disease, the main teenage-onset form of progressive myoclonus epilepsy (PME), and one of the severest epilepsies. Pathologically, a starch-like compound, polyglucosan, accumulates in neuronal cell bodies and overtakes neuronal small processes, mainly dendrites. Polyglucosan formation is catalyzed by glycogen synthase, which is activated through dephosphorylation by glycogen-associated protein phosphatase-1 (PP1). Here we remove PTG, one of the proteins that target PP1 to glycogen, from mice with Lafora disease. This results in near-complete disappearance of polyglucosans and in resolution of neurodegeneration and myoclonic epilepsy. This work discloses an entryway to treating this fatal epilepsy and potentially other glycogen storage diseases.

Original languageEnglish (US)
Article numbere1002037
JournalPLoS genetics
Volume7
Issue number4
DOIs
StatePublished - Apr 1 2011

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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    Turnbull, J., DePaoli-Roach, A. A., Zhao, X., Cortez, M. A., Pencea, N., Tiberia, E., Piliguian, M., Roach, P. J., Wang, P., Ackerley, C. A., & Minassian, B. A. (2011). PTG depletion removes lafora bodies and rescues the fatal epilepsy of lafora disease. PLoS genetics, 7(4), [e1002037]. https://doi.org/10.1371/journal.pgen.1002037