Glycosylphosphatidylinositol (GPI) is a posttranslational glycolipid modification of proteins that is widely conserved among eukaryotes. There are about 150 types of GPI-anchored proteins (GPI-APs) in mammalian cells. GPI is composed of a common core structure and side chains specific to different organisms. Free GPIs, or protein-unlinked GPIs, are present on some protozoan and mammalian cell surfaces. The biosynthetic pathway of the GPI side chain in mammalian cells has recently been determined and the relationships between free GPIs and some diseases have been identified. Therefore, GPI research is entering a new phase. Here, I introduce recent findings about GPI side chains and free GPIs in mammalian cells.

Microglia represent a population of resident immune cells in the central nervous system, and activation of microglia has long been considered to contribute to the neuroinflammation. However, recent analyses have indicated that activated microglia are phenotypically and functionally heterogeneous and have various roles in pathophysiological conditions. In addition, ramified microglia, also called “resting microglia”, are heterogeneous and have critical roles in the maintenance of homeostasis in the central nervous system. On the other hand, glycans are synthesized by a combination of multiple glycosyltransferases, and they play important roles in the central nervous system. Accumulating evidence suggests that distribution patterns of glycans in microglia may differ, based on the phenotypes. However, the relationship between microglial functions and glycans remains unclear. In this minireview, we summarize the potential involvement of keratan sulfate in the heterogeneity of microglia.

Intracellular or extracellular deposition of highly ordered fibrillar aggregates is a characteristic of protein misfolding diseases. Proteins can aggregate alone in vitro; however, deposits of fibrillar aggregates in vivo contain a number of proteinaceous and non-protein components in addition to the major protein that forms the aggregates. These components are thought to play critical roles in the pathology of protein misfolding diseases. Among these components, glycosaminoglycans (GAGs), which are heteropolysaccharides that occur in all mammalian tissues, are modified by sulfation that determines specific interactions between GAGs and their protein ligands. This mini-review summarizes our current understanding of how sulfated GAGs contribute to the pathology of protein misfolding diseases, with a particular focus on amyloidosis.

Glycosylphosphatidylinositol (GPI) is a posttranslational glycolipid modification of proteins that is widely conserved among eukaryotes. There are about 150 types of GPI-anchored proteins (GPI-APs) in mammalian cells. GPI is composed of a common core structure and side chains specific to different organisms. Free GPIs, or protein-unlinked GPIs, are present on some protozoan and mammalian cell surfaces. The biosynthetic pathway of the GPI side chain in mammalian cells has recently been determined and the relationships between free GPIs and some diseases have been identified. Therefore, GPI research is entering a new phase. Here, I introduce recent findings about GPI side chains and free GPIs in mammalian cells.

Microglia represent a population of resident immune cells in the central nervous system, and activation of microglia has long been considered to contribute to the neuroinflammation. However, recent analyses have indicated that activated microglia are phenotypically and functionally heterogeneous and have various roles in pathophysiological conditions. In addition, ramified microglia, also called “resting microglia”, are heterogeneous and have critical roles in the maintenance of homeostasis in the central nervous system. On the other hand, glycans are synthesized by a combination of multiple glycosyltransferases, and they play important roles in the central nervous system. Accumulating evidence suggests that distribution patterns of glycans in microglia may differ, based on the phenotypes. However, the relationship between microglial functions and glycans remains unclear. In this minireview, we summarize the potential involvement of keratan sulfate in the heterogeneity of microglia.

Intracellular or extracellular deposition of highly ordered fibrillar aggregates is a characteristic of protein misfolding diseases. Proteins can aggregate alone in vitro; however, deposits of fibrillar aggregates in vivo contain a number of proteinaceous and non-protein components in addition to the major protein that forms the aggregates. These components are thought to play critical roles in the pathology of protein misfolding diseases. Among these components, glycosaminoglycans (GAGs), which are heteropolysaccharides that occur in all mammalian tissues, are modified by sulfation that determines specific interactions between GAGs and their protein ligands. This mini-review summarizes our current understanding of how sulfated GAGs contribute to the pathology of protein misfolding diseases, with a particular focus on amyloidosis.