TY - JOUR
T1 - PTG depletion removes lafora bodies and rescues the fatal epilepsy of lafora disease
AU - Turnbull, Julie
AU - DePaoli-Roach, Anna A.
AU - Zhao, Xiaochu
AU - Cortez, Miguel A.
AU - Pencea, Nela
AU - Tiberia, Erica
AU - Piliguian, Mark
AU - Roach, Peter J.
AU - Wang, Peixiang
AU - Ackerley, Cameron A.
AU - Minassian, Berge A.
PY - 2011/4
Y1 - 2011/4
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pgen.1002037
DO - 10.1371/journal.pgen.1002037
M3 - Article
C2 - 21552327
AN - SCOPUS:79955634506
SN - 1553-7390
VL - 7
JO - PLoS genetics
JF - PLoS genetics
IS - 4
M1 - e1002037
ER -