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Loss of branched O-mannosyl glycans in astrocytes accelerates remyelination.
https://repo.qst.go.jp/records/46877
https://repo.qst.go.jp/records/468777a5f130d-3629-4063-b799-7cc7e33190c2
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2014-10-21 | |||||
タイトル | ||||||
タイトル | Loss of branched O-mannosyl glycans in astrocytes accelerates remyelination. | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Kanekiyo, Kenji
× Kanekiyo, Kenji× Inamori, Kei-ichiro× Kitazume, Shinobu× Sato, Keiko× Maeda, Jun× Higuchi, Makoto× Kizuka, Yasuhiko× Korekane, Hiroaki× Matsuo, Ichiro× Honke, Koichi× Taniguchi, Naoyuki× 前田 純× 樋口 真人 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | In demyelinating diseases such as multiple sclerosis, a critical problem is failure of remyelination, which is important for protecting axons against degeneration and restoring conduction deficits. However, the underlying mechanism of demyelination/remyelination remains unclear. N-acetylglucosaminyltransferase-IX (GnT-IX; also known as GnT-Vb) is a brain-specific glycosyltransferase that catalyzes the branched formation of O-mannosyl glycan structures. O-Mannosylation of α-dystroglycan is critical for its function as an extracellular matrix receptor, but the biological significance of its branched structures, which are exclusively found in the brain, is unclear. In this study, we found that GnT-IX formed branched O-mannosyl glycans on receptor protein tyrosine phosphatase β (RPTPβ) in vivo. Since RPTPβ is thought to play a regulatory role in demyelinating diseases, GnT-IX-deficient mice were subjected to cuprizone-induced demyelination. Cuprizone feeding for 8 weeks gradually promoted demyelination in wild-type mice. In GnT-IX-deficient mice, the myelin content in the corpus callosum was reduced after 4 weeks of treatment, but markedly increased at 8 weeks, suggesting enhanced remyelination under GnT-IX deficiency. Furthermore, astrocyte activation in the corpus callosum of GnT-IX-deficient mice was significantly attenuated, and an oligodendrocyte cell lineage analysis indicated that more oligodendrocyte precursor cells differentiated into mature oligodendrocytes. Together, branched O-mannosyl glycans in the corpus callosum in the brain are a necessary component of remyelination inhibition in the cuprizone-induced demyelination model, suggesting that modulation of O-mannosyl glycans is a likely candidate for therapeutic strategies. | |||||
書誌情報 |
The Journal of neuroscience : the official journal of the Society for Neuroscience 巻 33, 号 24, p. 10037-10047, 発行日 2013-06 |
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出版者 | ||||||
出版者 | Society for Neuroscience | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0270-6474 | |||||
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識別子タイプ | PMID | |||||
関連識別子 | 23761899 |