dSarm/Sarm1は,傷害によるアクソン死経路の活性化に必須です
Jeannette M Osterloh1, Jing Yang, Timothy M Rooney
1Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Science (New York, N.Y.)
|June 9, 2012
まとめ
ステリルなα/Armadillo/Toll-Interleukin受容体ホモロジードメインタンパク質 (Sarm1) 遺伝子の喪失は,損傷後の軸索の自己破壊を防ぐ. この発見は,アクソン死のための古くから保存された経路を明らかにし,神経損傷と神経変性疾患のための新しい治療標的を提供しています.
科学分野:
- 神経科学は神経科学である.
- 細胞生物学 細胞生物学
- 遺伝学 遺伝学とは
背景:
- 軸索性およびシナプス性退行は,外周神経症,脳損傷,神経変性疾患を含む様々な神経学的状態の重要な特徴です.
- 軸索変性症は,自己破壊プログラムが活発に行われていると考えられているが,このプロセスの強力な遺伝子ブロッカーは未だに捉えられないままである.
研究 の 目的:
- 軸索変性におけるドロソフィラトール受容体アダプタdSarmの役割を調査する.
- サルム1媒介のシグナル伝達が哺乳類に保存され,軸索死亡経路に寄与するかどうかを判断する.
主な方法:
- ドロソフィラdSarmの機能喪失変異を利用して,怪我後の軸索変性への影響を評価した.
- 切断されたマウスのSarm1ヌルアクソンの生存を,in vivoおよびin vitroモデルの両方で調べました.
主要な成果:
- ドロソフィラ細胞におけるdSarmの喪失は,アクソトミー後の長期間,ワレリアン変性自律的に抑制された.
- マウスでSarm1が欠けていたアクソンが切断され,インビヴォとインビトロの両方で,長期的な生存率が有意であることが示されました.
- これらの発見は,Sarm1シグナル伝達が損傷後の軸索破壊を積極的に促進し,種間で保存されていることを示しています.
結論:
- アクソンは,怪我後に自己破壊するメカニズムを持っている.
- ステリルなα/Armadillo/Toll-Interleukin受容体ホモロジードメインタンパク質 (Sarm1) は,古くから保存されている軸索死経路の重要な構成要素です.
- Sarm1をターゲットにすることは,軸索変性を含む状態のための潜在的な治療戦略を提示します.
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