Abstract

Abnormal carbohydrate structures known as polyglucosan bodies (PGBs) are associated with neurodegenerative disorders, glycogen storage diseases (GSDs), and aging. A hallmark of the GSD Lafora disease (LD), a fatal childhood epilepsy caused by recessive mutations in the EPM2A or EPM2B genes, are cytoplasmic PGBs known as Lafora bodies (LBs). LBs result from aberrant glycogen metabolism and drive disease progression. They are abundant in brain, muscle and heart of LD patients and Epm2a-/- and Epm2b-/- mice. LBs and PGBs are histologically reminiscent of starch, semicrystalline carbohydrates synthesized for glucose storage in plants. In this study, we define LB architecture, tissue-specific differences, and dynamics. We propose a model for how small polyglucosans aggregate to form LBs. LBs are very similar to PGBs of aging and other neurological disorders, and so these studies have direct relevance to the general understanding of PGB structure and formation.

Document Type

Article

Publication Date

4-14-2020

Notes/Citation Information

Published in Carbohydrate Polymers.

© 2020 Elsevier Ltd.

© 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/.

The document available for download is the authors' post-peer-review final draft of the article.

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.carbpol.2020.116260

Funding Information

This work was supported by the National Institutes of Health [R01 NS070899 to M.S.G., P01 NS097197 to M.S.G., R35 NS116824 to M.S.G., F31 NS093892 to M.K.B], an Epilepsy Foundation New Therapy Commercialization Grant to M.S.G., an award from the Mizutani Foundation for Glycoscience to M.S.G., and the Glyco@Alps program [ANR-15-IDEX-02]. M.K.B. has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement [No. 754510M]. M.A.S. is supported by a Mater Research McGuckin Early Career Fellowship, the University of Queensland’s Amplify Initiative and Mater Foundation.

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