Structure and Regulation of Glycogen Synthase in the Brain

Brain glycogen synthesis is a regulated, multi-step process that begins with glucose transport across the blood brain barrier and culminates with the actions of glycogen synthase and the glycogen branching enzyme to elongate glucose chains and introduce branch points in a growing glycogen molecule. This review focuses on the synthesis of glycogen in the brain, with an emphasis on glycogen synthase, but draws on salient studies in mammalian muscle and liver as well as baker's yeast, with the goal of providing a more comprehensive view of glycogen synthesis and highlighting potential areas for further study in the brain. In addition, deficiencies in the glycogen biosynthetic enzymes which lead to glycogen storage diseases in humans are discussed, highlighting effects on the brain and discussing findings in genetically modified animal models that recapitulate these diseases. Finally, implications of glycogen synthesis in neurodegenerative and other diseases that impact the brain are presented.