Editorial [ Glycobiological Approach to Neurological Disorders Guest Editor: Keiko Kato ]
The first glycobiology investigation into neurological disorders showed that ganglioside was a novel glycolipid in the brain of a Tay-Sachs patients in 1939. In the 1960's or later, the finding led to further glycobiology studies into neurological disorders. Advances in this area have continued at a steady rate during most of the twentieth century, based on investigations into the interactions of the highly complicated carbohydrate structures of glycoproteins and glycolipids with the physiological and structural complexity of brain. However, there has recently been an unparalleled explosion of new knowledge. There are many reasons for this acceleration of progress including; (1) collaborative studies using genetically engineered knock-out and knock-in mice along with classical biological and pharmacological approaches, (2) great technical advances in the mass spectroscopy of carbohydrates, and (3) accumulation of genomic and proteomic information, followed by molecular information regarding enzymes involved in sugar metabolism and in the sorting, processing and degradation of oligosaccharides, proteoglycans, and glycolipids. More recently, the important role of glycans has been underscored by the growing list of human diseases that result from defects and mutations in glycosylation.
The overall aim of the reviews in this issue is to highlight the most exciting information on glycobiological neurology, and developments in neuroprotective drugs that affect glycosylation and markers of diseases based on glycobiological approach. There has been an increased number of reports describing imbalances of sphingoglycolipids-cholesterol-rich membrane microdomains, or rafts causing disfunctions in brain, where sphingoglycolipids containing gangliosides are rich. The review by Mutoh et al. focuses on the involvements of sphingoglycolipids with risk factors for Alzheimer's diseases (AD) and proposals for glycobiological approaches as future therapies. Schengrund focuses on pathogens that affect the nervous system and require carbohydrates during any process of the infectious machinery. While there is a recent example of Tamiflu, an inhibitor of the enzyme neuraminidase (sialidase), which is effective for the treatment of influenza A and B in the peripheral system, there is little effective drug against pathogens in the nervous system. This review provides hints for the development of carbohydrate- based drugs against pathogens in the nervous system. Furthermore, Komagamine and Yuki focus on the latest findings about Guillain-Barre syndrome, characterized by auto-immune diseases induced following infection with C. jejuni. Concerning therapeutic approach, Sakuraba et al. describe very recent trials of enzyme-replacement therapy and the development of a brain-specific delivery system for several metabolic diseases that cause neurological disorders. Alternatively, Yu and Yanagisawa review knowledge of neural stem cells analyzed from a glycobiological dimension in order to use these as cell therapy in the future. The sialylated group possesses a negative charge at the terminal position of sugar linkages on sphingoglycolipids and glycoproteins. Sampathkumar et al. describe perspectives of sialic acids as diagnostic and therapeutic reagents for neurological disorders. Finally, Narimatsu et al. review the nervous symptoms of knock-out mice with targeted deletions of glycosyltransferase genes and their usefulness as animal models for neurological disorders. Taken together, the sharing of information concerning glycobiological neurology could facilitate explorations into novel drugs based on glycobiology to treat neurological diseases induced by a variety of causes, in addition to inborn errors that cause neurological disorders. I would like to thank Dr. Masao Iwamori for giving advice for determination of the present authors. I would like to thank Dr. Matthew Honan, the Editorial Director; Dr. Mark Varney, the Editor-in-Chief; Miss Saima Ghaffar Rao, the Manager Publications; and the staff at Bentham Science Publishers for their assistance, efforts and time.
Document Type: Research Article
Department of Structural and Functional Biosciences for Animals Graduate School of Life and Environmental Sciences Osaka Prefecture University Japan.
Publication date: August 1, 2006
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CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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