2006 Fiscal Year Final Research Report Summary
Functions of chondroitin sulfate polysaocharide in the central nervous system
| Project/Area Number |
14082210
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Institute for Developmental Research, Aichi Human Service Center |
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Principal Investigator |
OOHIRA Atsuhiko Institute for Developmental Research, Aichi Human Service Center, Dept. Perinatol., Department Head (20101074)
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| Project Period (FY) |
2002 – 2006
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| Keywords | chondroitin sulfate / proteoglycan / neuroglycan C / neural stem cell / brain / proliferation / neurite extension / cell death |
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| Research Abstract |
Functions of chondroitin sulfate proteoglycans (CSPGs) in the central nervous system were investigated in the two ways; functional analyses of a brain-specific CSPG, neuroglycan C (NGC), that we originally found in the developing rat brain and chondroitin sulfate (CS) polysaccharides as a major microenvironmental molecule of cells in the brain.
I. Functions of neuroglycan C
Site-directed mutagenesis revealed that a CS chain was introduced to S^<123> of the mouse NGC core protein. In addition to this CS-attachment domain, the extracellular region of NGC contains two other unique domains; a cluster of acidic amino acids (AA-domain) and an epidermal growth factor-like domain (EGF-domain). Both CS- and AA-domains had a high affinity to midkine, a growth factor. Both AA- and EGF- domains have a promotive activity for neurite extension. EGF-domain promotes growth of cells with EGF-receptors. Mouse strains with low and no expressions of NGC were produced. These mice show behavioral abnormalities. All these findings indicate that NGC is a functional molecule in the central nervous system.
II. Functions of chondroitin sulfate polysaccharides
CS polysaccharides isolated and purified from developing rat brains promote fibroblast growth factor (FGF)-2-mediated proliferation of neural stem cells. Commercial preparations of CS, CS-B and CS-E, also promote FGF-2-mediated neural stem cell growth, suggesting that an iduronic acid-containing structure (B-structure) and an over sulfated structure formed by GalNAc-4,6-disulfate (E-structure) in the CS polysaccharides are involved in this promotion of neural stem cell growth. Additionally, CS-E protects neurons from glutamate-induced excitatory neural cell death, that occurs immediately after brain injuries. Thus, CS polysaccharide is a bioactive molecule in the brain.
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[Journal Article] Academic Press, San Diego2006
Author(s)
Fumiko Matsui
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Journal Title
Isolation, purification, and analysis of chondroitin sulfate proteoglycans. in : Chondroitin Sulfate : Structure. Role and Phermacological Activity
Pages: 17
Description
「研究成果報告書概要(和文)」より
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[Journal Article] 共立出版2004
Author(s)
大平敦彦
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Journal Title
中枢神経系の発達および再生治療とコンドロイチン硫酸プロテオグリカン蛋白質核酸酵素(増刊)
Pages: 5
Description
「研究成果報告書概要(和文)」より
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