Next Article in Journal
Electronegative Low-Density Lipoprotein L5 Impairs Viability and NGF-Induced Neuronal Differentiation of PC12 Cells via LOX-1
Next Article in Special Issue
Contribution of Intrinsic Lactate to Maintenance of Seizure Activity in Neocortical Slices from Patients with Temporal Lobe Epilepsy and in Rat Entorhinal Cortex
Previous Article in Journal
Galectin-3 Performance in Histologic and Cytologic Assessment of Thyroid Nodules: A Systematic Review and Meta-Analysis
Previous Article in Special Issue
Mitochondrial Dysfunction Mediated by Poly(ADP-Ribose) Polymerase-1 Activation Contributes to Hippocampal Neuronal Damage Following Status Epilepticus
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessReview
Int. J. Mol. Sci. 2017, 18(8), 1743;

Pathogenesis of Lafora Disease: Transition of Soluble Glycogen to Insoluble Polyglucosan

Program in Genetics and Genome Biology, The Hospital for Sick Children Research Institute, 686 Bay Street, Toronto, ON M5G 0A4, Canada
Glycation and Diabetes, Mater Research Institute, Translational Research Institute, The University of Queensland, 37 Kent St., Woolloongabba, Brisbane 4102, Australia
The Impact Centre of the University of Toronto, 60 St. George Street, Toronto, ON M5S 1A7, Canada
Faculty of Mathematics and Science, University of Potsdam, 14476 Potsdam-Golm, Germany
Division of Neurology, Department of Pediatrics, University of Texas Southwestern, 5323 Harry Hines Blvd., Dallas, TX 75390-9063, USA
Author to whom correspondence should be addressed.
Academic Editor: Wolfram S. Kunz
Received: 17 July 2017 / Revised: 4 August 2017 / Accepted: 6 August 2017 / Published: 11 August 2017
Full-Text   |   PDF [2829 KB, uploaded 11 August 2017]   |  


Lafora disease (LD, OMIM #254780) is a rare, recessively inherited neurodegenerative disease with adolescent onset, resulting in progressive myoclonus epilepsy which is fatal usually within ten years of symptom onset. The disease is caused by loss-of-function mutations in either of the two genes EPM2A (laforin) or EPM2B (malin). It characteristically involves the accumulation of insoluble glycogen-derived particles, named Lafora bodies (LBs), which are considered neurotoxic and causative of the disease. The pathogenesis of LD is therefore centred on the question of how insoluble LBs emerge from soluble glycogen. Recent data clearly show that an abnormal glycogen chain length distribution, but neither hyperphosphorylation nor impairment of general autophagy, strictly correlates with glycogen accumulation and the presence of LBs. This review summarizes results obtained with patients, mouse models, and cell lines and consolidates apparent paradoxes in the LD literature. Based on the growing body of evidence, it proposes that LD is predominantly caused by an impairment in chain-length regulation affecting only a small proportion of the cellular glycogen. A better grasp of LD pathogenesis will further develop our understanding of glycogen metabolism and structure. It will also facilitate the development of clinical interventions that appropriately target the underlying cause of LD. View Full-Text
Keywords: lafora disease; laforin; malin; polyglucosan body; chain length distribution; glycogen phosphorylation lafora disease; laforin; malin; polyglucosan body; chain length distribution; glycogen phosphorylation

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Sullivan, M.A.; Nitschke, S.; Steup, M.; Minassian, B.A.; Nitschke, F. Pathogenesis of Lafora Disease: Transition of Soluble Glycogen to Insoluble Polyglucosan. Int. J. Mol. Sci. 2017, 18, 1743.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top