Polyglucosan body structure in Lafora disease

M. Kathryn Brewer, Jean Luc Putaux, Alberto Rondon, Annette Uittenbogaard, Mitchell A. Sullivan, Matthew S. Gentry

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Abnormal carbohydrate structures known as polyglucosan bodies (PGBs) are associated with neurological 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.

Original languageEnglish
Article number116260
JournalCarbohydrate Polymers
Volume240
DOIs
StatePublished - Jul 15 2020

Bibliographical note

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. We acknowledge the NanoBio-ICMG Platform (FR 2607, Grenoble, France) for granting access to the Electron Microscopy facility and Ziyi Wang for extracting the rat muscle glycogen, which was used as a reference sample for SEC. We also thank Xinle Tan for his technical assistance with SEC experiments, Robert Gilbert for providing access to SEC equipment, Dr. Carole Moncman, Dr. Thomas Wilkop and the UK Light Microscopy Core for technical support, and all members of the Gentry lab and Dr. Craig Vander Kooi for constructive discussions.

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 Sk?odowska-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. We acknowledge the NanoBio-ICMG Platform (FR 2607, Grenoble, France) for granting access to the Electron Microscopy facility and Ziyi Wang for extracting the rat muscle glycogen, which was used as a reference sample for SEC. We also thank Xinle Tan for his technical assistance with SEC experiments, Robert Gilbert for providing access to SEC equipment, Dr. Carole Moncman, Dr. Thomas Wilkop and the UK Light Microscopy Core for technical support, and all members of the Gentry lab and Dr. Craig Vander Kooi for constructive discussions.

Publisher Copyright:
© 2020 Elsevier Ltd

Keywords

  • Lafora bodies
  • Lafora disease
  • epilepsy
  • glycogen
  • glycogen storage disease
  • polyglucosan bodies
  • starch

ASJC Scopus subject areas

  • Organic Chemistry
  • Polymers and Plastics
  • Materials Chemistry

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