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Cells 2018, 7(8), 87;

Lafora Disease: A Ubiquitination-Related Pathology

Department of Biotechnology, Polytechnic University of Valencia, 46022 Valencia, Spain
Centro de Investigación Príncipe Felipe, 46012 Valencia, Spain
Centro de Investigación Biomédica en Red de Enfermedades Raras, (CIBERER), 46010 Valencia, Spain
Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones, Científicas, 46010 Valencia, Spain
Author to whom correspondence should be addressed.
Received: 3 July 2018 / Revised: 23 July 2018 / Accepted: 24 July 2018 / Published: 26 July 2018
(This article belongs to the Special Issue Ubiquitination in Health and Disease)
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Lafora disease (LD, OMIM254780) is a rare and fatal form of progressive myoclonus epilepsy (PME). Among PMEs, LD is unique because of the rapid neurological deterioration of the patients and the appearance in brain and peripheral tissues of insoluble glycogen-like (polyglucosan) inclusions, named Lafora bodies (LBs). LD is caused by mutations in the EPM2A gene, encoding the dual phosphatase laforin, or the EPM2B gene, encoding the E3-ubiquitin ligase malin. Laforin and malin form a functional complex that is involved in the regulation of glycogen synthesis. Thus, in the absence of a functional complex glycogen accumulates in LBs. In addition, it has been suggested that the laforin-malin complex participates in alternative physiological pathways, such as intracellular protein degradation, oxidative stress, and the endoplasmic reticulum unfolded protein response. In this work we review the possible cellular functions of laforin and malin with a special focus on their role in the ubiquitination of specific substrates. We also discuss here the pathological consequences of defects in laforin or malin functions, as well as the therapeutic strategies that are being explored for LD. View Full-Text
Keywords: Lafora disease; ubiquitination; malin; E3-ligase; proteostasis; glycogen accumulation Lafora disease; ubiquitination; malin; E3-ligase; proteostasis; glycogen accumulation

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García-Gimeno, M.A.; Knecht, E.; Sanz, P. Lafora Disease: A Ubiquitination-Related Pathology. Cells 2018, 7, 87.

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