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

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

Research output: Contribution to journalArticle

56 Citations (Scopus)

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
Article numbere1002037
JournalPLoS Genetics
Volume7
Issue number4
DOIs
StatePublished - Apr 2011

Fingerprint

Lafora Disease
epilepsy
Protein Phosphatase 1
Epilepsy
glycogen
Glycogen
phosphoprotein phosphatase
Progressive Myoclonic Epilepsy
phosphatase
Myoclonic Epilepsy
Glycogen Storage Disease
glycogen (starch) synthase
protein
Glycogen Synthase
Dendrites
Neurodegenerative Diseases
Starch
dephosphorylation
dendrites
neurodegenerative diseases

ASJC Scopus subject areas

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

Cite this

Turnbull, J., De Paoli-Roach, A., Zhao, X., Cortez, M. A., Pencea, N., Tiberia, E., ... 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

PTG depletion removes lafora bodies and rescues the fatal epilepsy of lafora disease. / Turnbull, Julie; De Paoli-Roach, Anna; Zhao, Xiaochu; Cortez, Miguel A.; Pencea, Nela; Tiberia, Erica; Piliguian, Mark; Roach, Peter; Wang, Peixiang; Ackerley, Cameron A.; Minassian, Berge A.

In: PLoS Genetics, Vol. 7, No. 4, e1002037, 04.2011.

Research output: Contribution to journalArticle

Turnbull, J, De Paoli-Roach, A, Zhao, X, Cortez, MA, Pencea, N, Tiberia, E, Piliguian, M, Roach, P, Wang, P, Ackerley, CA & Minassian, BA 2011, 'PTG depletion removes lafora bodies and rescues the fatal epilepsy of lafora disease', PLoS Genetics, vol. 7, no. 4, e1002037. https://doi.org/10.1371/journal.pgen.1002037
Turnbull, Julie ; De Paoli-Roach, Anna ; Zhao, Xiaochu ; Cortez, Miguel A. ; Pencea, Nela ; Tiberia, Erica ; Piliguian, Mark ; Roach, Peter ; Wang, Peixiang ; Ackerley, Cameron A. ; Minassian, Berge A. / PTG depletion removes lafora bodies and rescues the fatal epilepsy of lafora disease. In: PLoS Genetics. 2011 ; Vol. 7, No. 4.
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