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  1. C100 医学部/医学系研究科
  2. C100a 雑誌掲載論文
  3. 学術雑誌

Ablation of Keratan Sulfate Accelerates Early Phase Pathogenesis of ALS

http://hdl.handle.net/2237/25426
http://hdl.handle.net/2237/25426
688495a3-70f5-44e3-86a6-b2bf5042faf9
名前 / ファイル ライセンス アクション
journal_pone_0066969.pdf journal_pone_0066969.pdf (15.5 MB)
Item type 学術雑誌論文 / Journal Article(1)
公開日 2017-01-18
タイトル
タイトル Ablation of Keratan Sulfate Accelerates Early Phase Pathogenesis of ALS
言語 en
著者 Hirano, Kenichi

× Hirano, Kenichi

WEKO 68912

en Hirano, Kenichi

Search repository
Ohgomori, Tomohiro

× Ohgomori, Tomohiro

WEKO 68913

en Ohgomori, Tomohiro

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Kobayashi, Kazuyoshi

× Kobayashi, Kazuyoshi

WEKO 68914

en Kobayashi, Kazuyoshi

Search repository
Tanaka, Fumiaki

× Tanaka, Fumiaki

WEKO 68915

en Tanaka, Fumiaki

Search repository
Matsumoto, Tomohiro

× Matsumoto, Tomohiro

WEKO 68916

en Matsumoto, Tomohiro

Search repository
Natori, Takamitsu

× Natori, Takamitsu

WEKO 68917

en Natori, Takamitsu

Search repository
Matsuyama, Yukihiro

× Matsuyama, Yukihiro

WEKO 68918

en Matsuyama, Yukihiro

Search repository
Uchimura, Kenji

× Uchimura, Kenji

WEKO 68919

en Uchimura, Kenji

Search repository
Sakamoto, Kazuma

× Sakamoto, Kazuma

WEKO 68920

en Sakamoto, Kazuma

Search repository
Takeuchi, Hideyuki

× Takeuchi, Hideyuki

WEKO 68921

en Takeuchi, Hideyuki

Search repository
Hirakawa, Akihiro

× Hirakawa, Akihiro

WEKO 68922

en Hirakawa, Akihiro

Search repository
Suzumura, Akio

× Suzumura, Akio

WEKO 68923

en Suzumura, Akio

Search repository
Sobue, Gen

× Sobue, Gen

WEKO 68924

en Sobue, Gen

Search repository
Ishiguro, Naoki

× Ishiguro, Naoki

WEKO 68925

en Ishiguro, Naoki

Search repository
Imagama, Shiro

× Imagama, Shiro

WEKO 68926

en Imagama, Shiro

Search repository
Kadomatsu, Kenji

× Kadomatsu, Kenji

WEKO 68927

en Kadomatsu, Kenji

Search repository
アクセス権
アクセス権 open access
アクセス権URI http://purl.org/coar/access_right/c_abf2
権利
言語 en
権利情報 Copyright: (c) 2013 Hirano et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
抄録
内容記述 Biopolymers consist of three major classes, i.e., polynucleotides (DNA, RNA), polypeptides (proteins) and polysaccharides (sugar chains). It is widely accepted that polynucleotides and polypeptides play fundamental roles in the pathogenesis of neurodegenerative diseases. But, sugar chains have been poorly studied in this process, and their biological/clinical significance remains largely unexplored. Amyotrophic lateral sclerosis (ALS) is a motoneuron-degenerative disease, the pathogenesis of which requires both cell autonomous and non-cell autonomous processes. Here, we investigated the role of keratan sulfate (KS), a sulfated long sugar chain of proteoglycan, in ALS pathogenesis. We employed ALS model SOD1G93A mice and GlcNAc6ST-1−/− mice, which are KS-deficient in the central nervous system. Unexpectedly, SOD1G93AGlcNAc6ST-1−/− mice exhibited a significantly shorter lifespan than SOD1G93A mice and an accelerated appearance of clinical symptoms (body weight loss and decreased rotarod performance). KS expression was induced exclusively in a subpopulation of microglia in SOD1G93A mice, and became detectable around motoneurons in the ventral horn during the early disease phase before body weight loss. During this phase, the expression of M2 microglia markers was transiently enhanced in SOD1G93A mice, while this enhancement was attenuated in SOD1G93AGlcNAc6ST-1−/− mice. Consistent with this, M2 microglia were markedly less during the early disease phase in SOD1G93AGlcNAc6ST-1−/− mice. Moreover, KS expression in microglia was also detected in some human ALS cases. This study suggests that KS plays an indispensable, suppressive role in the early phase pathogenesis of ALS and may represent a new target for therapeutic intervention.
言語 en
内容記述タイプ Abstract
出版者
言語 en
出版者 PLOS
言語
言語 eng
資源タイプ
資源タイプresource http://purl.org/coar/resource_type/c_6501
タイプ journal article
出版タイプ
出版タイプ VoR
出版タイプResource http://purl.org/coar/version/c_970fb48d4fbd8a85
DOI
関連タイプ isVersionOf
識別子タイプ DOI
関連識別子 https://doi.org/10.1371/journal.pone.0066969
ISSN
収録物識別子タイプ EISSN
収録物識別子 1932-6203
書誌情報 en : PLOS ONE

巻 8, 号 6, p. e66969-e66969, 発行日 2013-06
著者版フラグ
値 publisher
URI
識別子 http://dx.doi.org/10.1371/journal.pone.0066969
識別子タイプ DOI
URI
識別子 http://hdl.handle.net/2237/25426
識別子タイプ HDL
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