Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada.
PLoS Genet. 2011 Apr;7(4):e1002037. doi: 10.1371/journal.pgen.1002037. Epub 2011 Apr 28.
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.
拉佛拉病是最常见的青少年起病的神经退行性疾病，也是进行性肌阵挛性癫痫（PME）的主要青少年起病形式之一，是最严重的癫痫之一。从病理学上讲，一种淀粉样化合物，聚葡聚糖，在神经元细胞体中积累并取代神经元小突起，主要是树突。聚葡聚糖的形成由糖原合酶催化，糖原合酶通过糖原相关蛋白磷酸酶-1（PP1）的去磷酸化而被激活。在这里，我们从小鼠的拉佛拉病中去除了将 PP1 靶向糖原的蛋白质之一，PTG。这导致聚葡聚糖几乎完全消失，神经退行性变和肌阵挛性癫痫得到缓解。这项工作揭示了治疗这种致命癫痫症以及潜在的其他糖原贮积症的途径。
