Abnormal glycogen chain length pattern, not hyperphosphorylation, is critical in Lafora disease
نویسندگان
چکیده
منابع مشابه
Abnormal glycogen chain length pattern, not hyperphosphorylation, is critical in Lafora disease
Lafora disease (LD) is a fatal progressive epilepsy essentially caused by loss-of-function mutations in the glycogen phosphatase laforin or the ubiquitin E3 ligase malin. Glycogen in LD is hyperphosphorylated and poorly hydrosoluble. It precipitates and accumulates into neurotoxic Lafora bodies (LBs). The leading LD hypothesis that hyperphosphorylation causes the insolubility was recently chall...
متن کاملGlycogen hyperphosphorylation underlies lafora body formation.
OBJECTIVE Glycogen, the largest cytosolic macromolecule, acquires solubility, essential to its function, through extreme branching. Lafora bodies are aggregates of polyglucosan, a long, linear, poorly branched, and insoluble form of glycogen. Lafora bodies occupy vast numbers of neuronal dendrites and perikarya in Lafora disease in time-dependent fashion, leading to intractable and fatal progre...
متن کاملLafora progressive myoclonus epilepsy: glycogen storage disease vs neurodegenerative disease.
Neurology 2012;79:21–22 Two disease mechanisms operate in Lafora progressive myoclonus epilepsy (Lafora PME) to produce 3 phenotypes (epilepsy, rapid neurologic deterioration, and Lafora polyglucosan inclusion bodies). These 2 disease mechanisms are 1) an error in glycogen metabolism and 2) neurodegeneration. The question is, which comes first and which is primary and more important in disease ...
متن کاملInhibiting glycogen synthesis prevents Lafora disease in a mouse model.
Lafora disease (LD) is a fatal progressive myoclonus epilepsy characterized neuropathologically by aggregates of abnormally structured glycogen and proteins (Lafora bodies [LBs]), and neurodegeneration. Whether LBs could be prevented by inhibiting glycogen synthesis and whether they are pathogenic remain uncertain. We genetically eliminated brain glycogen synthesis in LD mice. This resulted in ...
متن کاملGlycogen accumulation underlies neurodegeneration and autophagy impairment in Lafora disease.
Lafora disease is a fatal neurodegenerative condition characterized by the accumulation of abnormal glycogen inclusions known as Lafora bodies. It is an autosomal recessive disorder caused by mutations in either the laforin or malin gene. To study whether glycogen is primarily responsible for the neurodegeneration in Lafora disease, we generated malin knockout mice with impaired (totally or par...
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ژورنال
عنوان ژورنال: EMBO Molecular Medicine
سال: 2017
ISSN: 1757-4676,1757-4684
DOI: 10.15252/emmm.201707608