cPLA2-MAVSによるアストロサイト病原性活動の代謝制御
Chun-Cheih Chao1, Cristina Gutiérrez-Vázquez1, Veit Rothhammer2
1Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Cell
|December 10, 2019
まとめ
アストロサイトにおけるスフィンゴリピドの代謝は,細胞塩基フォスホリファーズA2 (cPLA2) とミトコンドリア抗ウイルスシグナルタンパク質 (MAVS) を活性化することによって,中枢神経系 (CNS) の炎症を誘発する. ミグルスタットという薬は これらの炎症経路を抑制する 有望な効果を示しています
科学分野:
- 神経免疫学
- 代謝経路について
- アストロサイト生物学
背景:
- 代謝は外周免疫に影響するが,中枢神経系 (CNS) の炎症におけるその役割は不明である.
- 恒星細胞は中枢神経の恒常性と病気において重要な役割を果たします.
研究 の 目的:
- アストロサイト媒介の中枢神経系炎症におけるスフィンゴリピド代謝の役割を調査する.
- 神経炎症と代謝を結びつける 分子メカニズムを特定する
主な方法:
- プロテオミクス,メタボロミクス,トランスクリプトミクス分析
- 実験的な自己免疫性脳内炎 (EAE) モデルでの障害研究.
- cPLA2,MAVS,HK2を含むタンパク質の相互作用を調査した.
主要な成果:
- アストロサイトにおけるスフィンゴリピドの代謝はcPLA2- MAVSの相互作用を活性化し,NF- kBによる中枢神経系の炎症を促進する.
- この相互作用はMAVS- HK2の結合を妨害し,乳酸の産生とニューロンのサポートを減少させます.
- Miglustatという既存の薬は,病原性アストロサイトの活動を抑制し,EAEの重症度を低下させた.
結論:
- CNSの炎症を誘発する新種の免疫代謝経路を定義した.
- 神経炎症における MAVS の新たな役割を特定しました
- Miglustatは,中枢神経系の炎症性疾患の治療の可能性を示しています.
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