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多発性硬化症におけるオリゴデンドロサイト生成の動態
Maggie S Y Yeung1, Mehdi Djelloul1, Embla Steiner1
1Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Nature
|January 25, 2019
まとめ
多発性硬化症では新しいオリゴデンドロサイト生成が増加するが,ほとんどの患者では失敗する. 病変におけるレミエリン化は,新しい細胞を含まない可能性があり,新しい治療目標を示唆する.
科学分野:
- 神経科学
- 免疫学
- 細胞生物学
背景:
- オリゴデンドロサイトは中枢神経系でミエリン殻を形成する.
- 多発性硬化症 (MS) は免疫媒介によるミエリン破壊を含み,再生の可能性があります.
- ネズミのモデルでは,新しいオリゴデンドロサイトがミエリンを再生することを示しているが,ヒトの関連性は不明である.
研究 の 目的:
- ヒトの多発性硬化症におけるオリゴデンドロサイト生成のダイナミクスを調査する.
- 動物モデルがヒトのリミエリン化プロセスを正確に反映しているかどうかを評価する.
主な方法:
- オリゴデンドロサイトまでゲノムDNAに統合された 核実験から14Cを活用した.
- 多発性硬化症患者の正常に見える白質と影状プラークのオリゴデンドロサイト生成を分析した.
主要な成果:
- オリゴデンドロサイト生成は,攻撃的なMS症例では有意に増加したが,ほとんどの患者ではそうではなかった.
- MSの影状プラークのオリゴデンドロサイトは,新しく生成されたものではなく,古いものであることが判明しました.
- これは,多くのMS患者におけるオリゴデンドロサイト生成の潜在的欠陥を示しています.
結論:
- MSにおけるオリゴデンドロサイト生成の動態は予想外であり,動物モデルとは異なる.
- MSの病変におけるレミエリン化は,新しいオリゴデンドロサイトの形成を伴わない場合があります.
- 発見により,リミエリン化を標的とした現在のMS治療法の再評価と新たな治療法の開発が必要となる.
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