title: PTG depletion removes Lafora bodies and rescues the fatal epilepsy of Lafora disease.
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.
authors.affiliation: Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Turnbull
authors.forename: Anna A
authors.initials: AA
authors.lastname: DePaoli-Roach
authors.forename: Xiaochu
authors.initials: X
authors.lastname: Zhao
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Cortez
authors.forename: Nela
authors.initials: N
authors.lastname: Pencea
authors.forename: Erica
authors.initials: E
authors.lastname: Tiberia
authors.forename: Mark
authors.initials: M
authors.lastname: Piliguian
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Roach
authors.forename: Peixiang
authors.initials: P
authors.lastname: Wang
authors.forename: Cameron A
authors.initials: CA
authors.lastname: Ackerley
authors.forename: Berge A
authors.initials: BA
authors.lastname: Minassian
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology; D004195:Disease Models, Animal; D005936:Glucans / Q000032:analysis / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020192:Lafora Disease / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D005936:Glucans; D047908:Intracellular Signaling Peptides and Proteins; C104748:Ppp1r3c protein, mouse; C083094:polyglucosan; D006006:Glycogen Synthase