Potential therapeutic application of chondroitin sulfate/dermatan sulfate.
Glycosaminoglycans (GAGs) are complex polysaccharides, which play important roles in cell growth, differentiation, morphogenesis, cell migration, and bacterial/viral infections. Major GAGs include heparin (Hep)/heparan sulfate, and chondroitin sulfate (CS)/dermatan sulfate (DS). Hep has been used for the treatment of thromboembolic disorders for more than 75 years, and has an established position in therapy today. CS/DS has attracted less attention and its clinical use is limited. However, CS/DS also have intriguing biological activities, which in turn should help in the development of CS/DS-based therapeutics. In this review, the following potential applications of CS/DS chains are discussed. (1) Sugar drugs for parasitic and viral infections. Particular CS variants appear to be involved in infections of various microbes, suggesting that CS/DS oligosaccharide sequences specifically interacting with microbes will lead to the development of inhibitory drugs for these infections. (2) Regenerative medicine. Biological activities of CS/DS chains possibly involve various growth factors, also known as Hep-binding growth factors. Specific CS/DS chains recruit growth/neurotrophic factors and/or potentiate their activities, suggesting that minute amounts of functional CS/DS chains can be utilized for tissue regeneration instead of signaling proteins. (3) Anti-tumor drugs. Specific saccharide structures in CS/DS chains appear to be involved in tumor cell proliferation and metastasis. The detection and identification of such CS/DS saccharide sequences would be an important contribution to cancer therapy.
Yamada
Shuhei
S
Laboratory of Proteoglycan Signaling and Therapeutics, Frontier Research Center for Post-Genomic Science and Technology, Hokkaido University Graduate School of Life Science, Nishi 11-choume, Kita 21-jo, Kita-ku, Sapporo, Hokkaido 001-0021, Japan.
Sugahara
Kazuyuki
K
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002809:Chondroitin Sulfates / Q000737:chemistry / Q000627:therapeutic use*; D003871:Dermatan Sulfate / Q000737:chemistry / Q000627:therapeutic use*; D055808:Drug Discovery; D006025:Glycosaminoglycans / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007239:Infections / Q000188:drug therapy; D008115:Liver Regeneration; D009369:Neoplasms / Q000188:drug therapy; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D010003:Osteoarthritis / Q000188:drug therapy
D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D006025:Glycosaminoglycans; D003871:Dermatan Sulfate; D002809:Chondroitin Sulfates