Pathogenesis of Lafora Disease: Transition of Soluble Glycogen to Insoluble Polyglucosan
AbstractLafora 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
Scifeed alert for new publicationsNever miss any articles matching your research from any publisher
- Get alerts for new papers matching your research
- Find out the new papers from selected authors
- Updated daily for 49'000+ journals and 6000+ publishers
- Define your Scifeed now
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.
Sullivan MA, Nitschke S, Steup M, Minassian BA, Nitschke F. Pathogenesis of Lafora Disease: Transition of Soluble Glycogen to Insoluble Polyglucosan. International Journal of Molecular Sciences. 2017; 18(8):1743.Chicago/Turabian Style
Sullivan, Mitchell A.; Nitschke, Silvia; Steup, Martin; Minassian, Berge A.; Nitschke, Felix. 2017. "Pathogenesis of Lafora Disease: Transition of Soluble Glycogen to Insoluble Polyglucosan." Int. J. Mol. Sci. 18, no. 8: 1743.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.