Glycogen metabolism and lafora disease

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Scopus citations

Abstract

Lafora disease is a juvenile-onset, fatal epilepsy that is characterized by the formation of Lafora bodies in many tissues, including skeletal muscle, heart, and neurons. Lafora bodies are insoluble deposits that contain polyglucosan, a poorly branched form of glycogen, and associated proteins. Evidence is mounting that Lafora bodies either cause or contribute to the pathology of the disease. It is a genetic disease caused by mutation in one of two genes, EPM2A and EPM2B, which encode, respectively, a phosphatase called laforin and an E3 ubiquitin ligase called malin. Laforin is a phosphatase of the atypical dual specificity phosphatase subfamily that, in vitro and in vivo, removes phosphate monoesters from glycogen. Normal glycogen contains trace amounts of phosphate introduced as a minor side reaction by the synthetic enzyme, glycogen synthase. In laforin knockout mice, glycogen becomes hyperphosphorylated and, as the mice age, acquires structural abnormalities and the tendency to come out of solution, consistent with Lafora body formation. Mutation of malin or laforin results in similar symptoms in patients and malin and laforin knockout mice exhibit phenotypic similarity in terms of neurological defects and abnormal glycogen metabolism, including hyperphosphorylation and Lafora body formation.

Original languageEnglish (US)
Title of host publicationProtein Tyrosine Phosphatase Control of Metabolism
PublisherSpringer New York
Pages239-262
Number of pages24
ISBN (Electronic)9781461478553
ISBN (Print)1461478545, 9781461478546
DOIs
StatePublished - Apr 1 2013

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Roach, P. J., & Depaoli-Roach, A. A. (2013). Glycogen metabolism and lafora disease. In Protein Tyrosine Phosphatase Control of Metabolism (pp. 239-262). Springer New York. https://doi.org/10.1007/978-1-4614-7855-3_13