Brain Glycogen Structure and Its Associated Proteins: Past, Present and Future

Abstract

This chapter reviews the history of glycogen-related research and discusses in detail the structure, regulation, chemical properties and subcellular distribution of glycogen and its associated proteins, with particular focus on these aspects in brain tissue.

From Prokaryotes to Eukaryotes: Insights Into the Molecular Structure of Glycogen Particles

“…Further exploration of these binding proteins in the glycogen proteome facilitates the understanding of the dynamic nature and cellular distribution of glycogen particles. In addition, glycogen proteomes in adipocyte and brain were also studied, which led to the discovery of novel glycogen-protein associations, indicating cell-specific differences in glycogen metabolism ( Stapleton et al, 2013 ; Brewer and Gentry, 2019 ). Although the fine structure of glycogen molecules in C. elegans is recently reported, there is still no study focusing on its glycogen proteome ( Liu et al, 2020a ).…”

“…Glycogen was initially discovered in animal liver by Bernard ( Young, 1957 ) and later by Revel (1964) . Soon after that, Sanson isolated glycogen from spleen, muscle, and kidney of a horse ( Brewer and Gentry, 2019 ). A variety of other organs and tissues also contain glycogen particles, such as heart ( Mowry and Bangle, 1951 ; Besford et al, 2012 ), brain ( Brewer and Gentry, 2019 ), retina ( Samorajski et al, 1965 ), pancreas ( Brereton et al, 2016 ), uterus ( Dean, 2019 ), fallopian tubes ( Dean, 2019 ), vagina ( Amabebe and Anumba, 2018 ), embryos ( Daimon, 1977 ) and adipocytes ( Ceperuelo-Mallafré et al, 2016 ).…”

“…Soon after that, Sanson isolated glycogen from spleen, muscle, and kidney of a horse ( Brewer and Gentry, 2019 ). A variety of other organs and tissues also contain glycogen particles, such as heart ( Mowry and Bangle, 1951 ; Besford et al, 2012 ), brain ( Brewer and Gentry, 2019 ), retina ( Samorajski et al, 1965 ), pancreas ( Brereton et al, 2016 ), uterus ( Dean, 2019 ), fallopian tubes ( Dean, 2019 ), vagina ( Amabebe and Anumba, 2018 ), embryos ( Daimon, 1977 ) and adipocytes ( Ceperuelo-Mallafré et al, 2016 ). In addition, some types of cells accumulate glycogen for different but important physiological purposes too, which include but not limited to macrophages ( Ma et al, 2020 ), lymphocytes ( Astaldi and Verga, 1957 ), erythrocytes ( Moses et al, 1972 ), neurons ( Saez et al, 2014 ), oncocytes ( Zois and Harris, 2016 ) and astrocytes ( Robert et al, 2001 ; Castejon et al, 2009 ).…”

“…Glycogen is a highly branched polysaccharide that is widely distributed across species from prokaryotes to eukaryotes ( Wilson et al, 2010 ), which plays pivotal roles in a variety of extremely important functions, such as energy reserve ( Greenberg et al, 2006 ), osmotic pressure maintenance ( Brown, 2004 ), host colonization ( Jones et al, 2008 ), blood glucose homeostasis ( Han et al, 2016 ), pH maintenance ( Fredricks et al, 2014 ) and tumor development ( Zhang et al, 2020 ). Since its first discovery by the French physiologist Claude Bernard in 1857, the structure and function of glycogen have been extensively characterized over the centuries, which leads to the grants of multiple Nobel prizes ( Brewer and Gentry, 2019 ). Although glycogen has multi-facet roles, its function is intrinsically determined by its unique structure ( Meléndez-Hevia et al, 1993 ; Wang and Wise, 2011 ).…”

Generation and characterization of a laforin nanobody inhibitor

“…Nearly all tissues metabolize glycogen and recent work has focused on the importance of glycogen metabolism in the brain 2 . Characterization of the enzymes and mechanisms of glycogen metabolism began over 70 years ago and include: synthesis by glycogen synthase, branching via glycogen branching enzyme, hydrolysis by glycogen phosphorylase, and debranching via glycogen debranching enzyme 3 . Over the last 20 years, a previously unknown protein called laforin has emerged as an important contributor to glycogen metabolism homeostasis.…”