Polyglucosan body structure in Lafora disease

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

doi:10.1016/j.carbpol.2020.116260

Polyglucosan body structure in Lafora disease

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

Producción científica: Article › revisión exhaustiva

29 Citas (Scopus)

Resumen

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.

Idioma original	English
Número de artículo	116260
Publicación	Carbohydrate Polymers
Volumen	240
DOI	https://doi.org/10.1016/j.carbpol.2020.116260
Estado	Published - jul 15 2020

Nota bibliográfica

Publisher Copyright:
© 2020 Elsevier Ltd

Financiación

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. 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\u2019s Horizon 2020 research and innovation programme under the Marie Sk\u0142odowska-Curie grant agreement [No. 754510M ]. M.A.S. is supported by a Mater Research McGuckin Early Career Fellowship , the University of Queensland\u2019s 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.

Financiadores	Número del financiador
Epilepsy Foundation New Therapy Commercialization
University of Queensland's Amplify Initiative
University of Queensland’s Amplify Initiative
Mater Research McGuckin
Horizon 2020
Marie Skłodowska-Curie fellowship	754510M
Mater Foundation	FR 2607
Mater Foundation
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council	R01NS070899, R35NS116824, P01NS097197
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council
National Institutes of Health (NIH)	F31 NS093892
National Institutes of Health (NIH)
Mizutani Foundation for Glycoscience	ANR-15-IDEX-02
Mizutani Foundation for Glycoscience
Horizon 2020 Framework Programme	754510
Horizon 2020 Framework Programme

ASJC Scopus subject areas

Organic Chemistry
Polymers and Plastics
Materials Chemistry

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10.1016/j.carbpol.2020.116260

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title = "Polyglucosan body structure in Lafora disease",

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.",

keywords = "Lafora bodies, Lafora disease, epilepsy, glycogen, glycogen storage disease, polyglucosan bodies, starch",

author = "Brewer, \{M. Kathryn\} and Putaux, \{Jean Luc\} and Alberto Rondon and Annette Uittenbogaard and Sullivan, \{Mitchell A.\} and Gentry, \{Matthew S.\}",

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AU - Rondon, Alberto

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AU - Sullivan, Mitchell A.

AU - Gentry, Matthew S.

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N2 - 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.

AB - 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.

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KW - Lafora disease

KW - epilepsy

KW - glycogen

KW - glycogen storage disease

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Polyglucosan body structure in Lafora disease

Resumen

Nota bibliográfica

Financiación

ASJC Scopus subject areas

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