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NOVEL HYALURONIDASE INHIBITORS FOR THE PROMOTION OF REMYELINATION

NOVEL HYALURONIDASE INHIBITORS FOR THE PROMOTION OF REMYELINATION
用于促进髓鞘再生的新型透明质酸酶抑制剂
批准号:
8357867
负责人:
Larry S. Sherman
金额:
$5.82万
依托单位国家:
美国
项目类别:
财政年份:
2011
资助国家:
美国
项目状态:
已结题
起止时间:
2011-05-01 至 2012-04-30

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中文摘要
翻译
这个子项目是利用这些资源的众多研究子项目之一
英文摘要
This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Oligodendrocyte progenitor cells (OPCs) can become myelin-forming oligodendrocytes (OLs) in the central nervous system (CNS). OPCs migrate to demyelinating lesions in patients with multiple sclerosis (MS) but often fail to mature into OLs that remyelinate demyelinated axons. Remyelination failure leads to long-term neurological deficits in MS patients. We previously found that a polysaccharide called hyaluronan (HA) accumulates in MS patient lesions. Our preliminary data indicate that OPCs express hyaluronidases, enzymes that break-down HA, and that breakdown products of HA inhibit the maturation of OPCs into myelin-forming OLs. Furthermore, these HA breakdown products inhibit remyelination and a drug that inhibits hyaluronidase activity can promote OPC maturation in vitro. Our hypothesis is that remyelination failure can be reversed by pharmacologically blocking hyaluronidase activity. Here, we aim to: (1) Identify indole carboxamide and other derivatives that inhibit hyaluronidase activity and promote OPC maturation in vitro. (2) Test if systemic suppression of hyaluronidase activity promotes remyelination in mice with experimentally-induced demyelinating diseases.
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会议论文
Hyaluron as a regulator of chemotherapy-induced changes in neurogenesis
ROLE OF EXTRACELLULAR MATRIX IN HYPOXIC-ISCHEMIC PERINATAL WHITE MATTER INJURY
COLLABORATIVE MS RESEARCH CENTER AWARD
EFFECTS OF HYALURONAN ON NEURAL STEM CELL HOMING AND DIFFERENTIATION
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