PTG protein depletion rescues malin-deficient Lafora disease in mouse

Julie Turnbull, Jonathan R. Epp, Danielle Goldsmith, Xiaochu Zhao, Nela Pencea, Peixiang Wang, Paul W. Frankland, Cameron A. Ackerley, Berge A. Minassian

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Ubiquitin ligases regulate quantities and activities of target proteins, often pleiotropically. The malin ubiquitin E3 ligase is reported to regulate autophagy, the misfolded protein response, microRNA silencing, Wnt signaling, neuronatin-mediated endoplasmic reticulum stress, and the laforin glycogen phosphatase. Malin deficiency causes Lafora disease, pathologically characterized by neurodegeneration and accumulations of malformed glycogen (Lafora bodies). We show that reducing glycogen production in malin-deficient mice by genetically removing PTG, a glycogen synthesis activator protein, nearly completely eliminates Lafora bodies and rescues the neurodegeneration, myoclonus, seizure susceptibility, and behavioral abnormality. Glycogen synthesis downregulation is a potential therapy for the fatal adolescence onset epilepsy Lafora disease. Ann Neurol 2014;75:442-446

Original languageEnglish (US)
Pages (from-to)442-446
Number of pages5
JournalAnnals of Neurology
Volume75
Issue number3
DOIs
StatePublished - Mar 2014

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Turnbull, J., Epp, J. R., Goldsmith, D., Zhao, X., Pencea, N., Wang, P., Frankland, P. W., Ackerley, C. A., & Minassian, B. A. (2014). PTG protein depletion rescues malin-deficient Lafora disease in mouse. Annals of Neurology, 75(3), 442-446. https://doi.org/10.1002/ana.24104