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

• Published in: PLoS genetics Vol. 7; no. 4; p. e1002037
• Main Authors: Turnbull, Julie, DePaoli-Roach, Anna A, Zhao, Xiaochu, Cortez, Miguel A, Pencea, Nela, Tiberia, Erica, Piliguian, Mark, Roach, Peter J, Wang, Peixiang, Ackerley, Cameron A, Minassian, Berge A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-04-2011; Public Library of Science (PLoS)
• Subjects: Animals; Biology; Brain - physiopathology; Carbohydrates; Degeneration; Disease; Disease Models, Animal; Enzymes; Epilepsy; Glucans - analysis; Glucans - metabolism; Glucose; Glycogen; Glycogen Synthase - metabolism; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - metabolism; Lafora Disease - genetics; Lafora Disease - physiopathology; Medical research; Medicine; Mice; Mice, Knockout; Microscopy; Mutation; Nervous system; Neurodegeneration; Physiological aspects; Proteins; Canada; United States
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1002037

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.