An inhibitor of chondroitin sulfate proteoglycan synthesis promotes central nervous system remyelination
書誌事項
- 公開日
- 2016-04-26
- 権利情報
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- https://creativecommons.org/licenses/by/4.0
- https://creativecommons.org/licenses/by/4.0
- DOI
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- 10.1038/ncomms11312
- 公開者
- Springer Science and Business Media LLC
説明
<jats:title>Abstract</jats:title> <jats:p> Remyelination is the generation of new myelin sheaths after injury facilitated by processes of differentiating oligodendrocyte precursor cells (OPCs). Although this repair phenomenon occurs in lesions of multiple sclerosis patients, many lesions fail to completely remyelinate. A number of factors have been identified that contribute to remyelination failure, including the upregulated chondroitin sulfate proteoglycans (CSPGs) that comprise part of the astrogliotic scar. We show that <jats:italic>in vitro</jats:italic> , OPCs have dramatically reduced process outgrowth in the presence of CSPGs, and a medication library that includes a number of recently reported OPC differentiation drugs failed to rescue this inhibitory phenotype on CSPGs. We introduce a novel CSPG synthesis inhibitor to reduce CSPG content and find rescued process outgrowth from OPCs <jats:italic>in vitro</jats:italic> and accelerated remyelination following focal demyelination in mice. Preventing CSPG deposition into the lesion microenvironment may be a useful strategy to promote repair in multiple sclerosis and other neurological disorders. </jats:p>
収録刊行物
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- Nature Communications
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Nature Communications 7 (1), 11312-, 2016-04-26
Springer Science and Business Media LLC
