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

27 Citations (Scopus)

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 - Jan 1 2014

Fingerprint

Lafora Disease
Glycogen
Proteins
Myoclonus
Endoplasmic Reticulum Stress
Ubiquitin-Protein Ligases
Autophagy
Ligases
Ubiquitin
MicroRNAs
Phosphoric Monoester Hydrolases
Epilepsy
Seizures
Down-Regulation

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Turnbull, J., Epp, J. R., Goldsmith, D., Zhao, X., Pencea, N., Wang, P., ... 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

PTG protein depletion rescues malin-deficient Lafora disease in mouse. / Turnbull, Julie; Epp, Jonathan R.; Goldsmith, Danielle; Zhao, Xiaochu; Pencea, Nela; Wang, Peixiang; Frankland, Paul W.; Ackerley, Cameron A.; Minassian, Berge A.

In: Annals of Neurology, Vol. 75, No. 3, 01.01.2014, p. 442-446.

Research output: Contribution to journalArticle

Turnbull, J, Epp, JR, Goldsmith, D, Zhao, X, Pencea, N, Wang, P, Frankland, PW, Ackerley, CA & Minassian, BA 2014, 'PTG protein depletion rescues malin-deficient Lafora disease in mouse', Annals of Neurology, vol. 75, no. 3, pp. 442-446. https://doi.org/10.1002/ana.24104
Turnbull J, Epp JR, Goldsmith D, Zhao X, Pencea N, Wang P et al. PTG protein depletion rescues malin-deficient Lafora disease in mouse. Annals of Neurology. 2014 Jan 1;75(3):442-446. https://doi.org/10.1002/ana.24104
Turnbull, Julie ; Epp, Jonathan R. ; Goldsmith, Danielle ; Zhao, Xiaochu ; Pencea, Nela ; Wang, Peixiang ; Frankland, Paul W. ; Ackerley, Cameron A. ; Minassian, Berge A. / PTG protein depletion rescues malin-deficient Lafora disease in mouse. In: Annals of Neurology. 2014 ; Vol. 75, No. 3. pp. 442-446.
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