Versican is a large chondroitin sulfate proteoglycan in the extracellular matrix (ECM). In adults, it is constitutively expressed in large arteries and the brain, serving as a structural macromolecule of the ECM. In embryos, it is transiently expressed at high levels in the developing heart, cartilage primordium, dermis, and hair follicles. In the inflammation and cancer invasion, versican is transiently expressed in the stroma. There, versican plays a major role in forming a “provisional matrix.” When the provisional matrix is replaced by the authentic extracellular matrix that should be, transiently expressed versican is primarily degraded by A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS)-1, 4, 5, 9, 15, 20 15, 20, and an N-terminal cleaved fragment serves as a bioactive molecule, thereby termed versikine. This paper reviews the biological functions of versican and its degradation products.

The structure-modified compound sulfoquinovosyl-acylpropanediol (SQAP), a derivative of sulfoquinovosyl-acylglycerol (SQAG) initially isolated as a DNA polymerase inhibitor in eukaryotic organisms. Malignant Tumor Treatment Technologies, Inc. (M.T.3) was received approval for the production and sale of animal medicinal products as LAVURCHIN from the Ministry of Agriculture, Forestry, and Fisheries of Japan on September 15, 2023. Currently, we are aiming to apply it to human treatment. SQAP exhibited anticancer activity as a single agent, however, its practical application was hindered by the necessity of high dosages. However, irradiation demonstrated a potent anticancer effect on animal samples of which dose level had been administered with non-anticancer levels of the compound. This led to the initiation of its development as a radiosensitizer.

Hyaluronan, a large linear glycopolymer, is a major component of the extracellular matrix (ECM) and is abundant in both the blood and lymph fluids. Its diverse biological functions have been investigated with deficient mouse in enzymes responsible for synthesis, binding, and degradation. Recently, the enzymes responsible for the extracellular degradation of hyaluronan, specifically cell migration-inducing protein (CEMIP)/HYBID and transmembrane protein-2 (TMEM2)/CEMIP2, have been identified. These enzymes were previously considered to have missing links in the hyaluronan metabolism and their discovery has garnered significant attention owing to their biological importance. This article focuses on the hyaluronidases responsible for hyaluronan degradation, emphasizing the differences between TMEM2/CEMIP2, a transmembrane hyaluronan-degrading enzyme, and other previously characterized hyaluronidases. Additionally, this article presents the cellular responses associated with the extracellular hyaluronan degradation activity, as reported in the literature.

Fucosylation is a post-translational modification that involves addition of L-fucose sugar to N-acetylglucosamine or galactose residues of glycoconjugates. The increased complexity and diversity of glycan complexes afforded by fucosylation contributes to distinct features of cell surfaces for self-recognition and communication with other cells. Aberrant expression of enzymes that drive fucosylation is linked to impaired cell–cell interactions under various physiological circumstances. Several aspects of this impairment are well-established in cancer and immune responses, but whether fucosyltransferases (FUTs), particularly α1,3-FUTs, which are abundantly expressed during embryogenesis, play a significant role in brain development is unclear. In this review, we consider recent findings concerning the roles of α1,3-FUTs in the developing and adult brain, as well as how these enzymes could be associated with neuropsychiatric disorders.

Versican is a large chondroitin sulfate proteoglycan in the extracellular matrix (ECM). In adults, it is constitutively expressed in large arteries and the brain, serving as a structural macromolecule of the ECM. In embryos, it is transiently expressed at high levels in the developing heart, cartilage primordium, dermis, and hair follicles. In the inflammation and cancer invasion, versican is transiently expressed in the stroma. There, versican plays a major role in forming a “provisional matrix.” When the provisional matrix is replaced by the authentic extracellular matrix that should be, transiently expressed versican is primarily degraded by A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS)-1, 4, 5, 9, 15, 20 15, 20, and an N-terminal cleaved fragment serves as a bioactive molecule, thereby termed versikine. This paper reviews the biological functions of versican and its degradation products.

The structure-modified compound sulfoquinovosyl-acylpropanediol (SQAP), a derivative of sulfoquinovosyl-acylglycerol (SQAG) initially isolated as a DNA polymerase inhibitor in eukaryotic organisms. Malignant Tumor Treatment Technologies, Inc. (M.T.3) was received approval for the production and sale of animal medicinal products as LAVURCHIN from the Ministry of Agriculture, Forestry, and Fisheries of Japan on September 15, 2023. Currently, we are aiming to apply it to human treatment. SQAP exhibited anticancer activity as a single agent, however, its practical application was hindered by the necessity of high dosages. However, irradiation demonstrated a potent anticancer effect on animal samples of which dose level had been administered with non-anticancer levels of the compound. This led to the initiation of its development as a radiosensitizer.

Hyaluronan, a large linear glycopolymer, is a major component of the extracellular matrix (ECM) and is abundant in both the blood and lymph fluids. Its diverse biological functions have been investigated with deficient mouse in enzymes responsible for synthesis, binding, and degradation. Recently, the enzymes responsible for the extracellular degradation of hyaluronan, specifically cell migration-inducing protein (CEMIP)/HYBID and transmembrane protein-2 (TMEM2)/CEMIP2, have been identified. These enzymes were previously considered to have missing links in the hyaluronan metabolism and their discovery has garnered significant attention owing to their biological importance. This article focuses on the hyaluronidases responsible for hyaluronan degradation, emphasizing the differences between TMEM2/CEMIP2, a transmembrane hyaluronan-degrading enzyme, and other previously characterized hyaluronidases. Additionally, this article presents the cellular responses associated with the extracellular hyaluronan degradation activity, as reported in the literature.

Fucosylation is a post-translational modification that involves addition of L-fucose sugar to N-acetylglucosamine or galactose residues of glycoconjugates. The increased complexity and diversity of glycan complexes afforded by fucosylation contributes to distinct features of cell surfaces for self-recognition and communication with other cells. Aberrant expression of enzymes that drive fucosylation is linked to impaired cell–cell interactions under various physiological circumstances. Several aspects of this impairment are well-established in cancer and immune responses, but whether fucosyltransferases (FUTs), particularly α1,3-FUTs, which are abundantly expressed during embryogenesis, play a significant role in brain development is unclear. In this review, we consider recent findings concerning the roles of α1,3-FUTs in the developing and adult brain, as well as how these enzymes could be associated with neuropsychiatric disorders.