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

PLoS Genet. 2011 Apr;7(4):e1002037. doi: 10.1371/journal.pgen.1002037. Epub 2011 Apr 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / physiopathology
  • Disease Models, Animal
  • Glucans / analysis
  • Glucans / metabolism*
  • Glycogen Synthase / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lafora Disease / genetics
  • Lafora Disease / physiopathology*
  • Mice
  • Mice, Knockout

Substances

  • Glucans
  • Intracellular Signaling Peptides and Proteins
  • Ppp1r3c protein, mouse
  • polyglucosan
  • Glycogen Synthase