老化した膠質細胞の除去は,タウに依存した病変と認知の低下を防ぐ

Tyler J Bussian¹, Asef Aziz², Charlton F Meyer²

¹Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.

Nature

|September 21, 2018

まとめ

細胞老化は神経変性や認知の衰えを引き起こしますマウスモデルでの老化細胞の除去は,タウ病変とニューロンの損失を防止し,セノリチクスを潜在的な治療法として示唆しています.

科学分野:

神経科学
細胞生物学
ゲロントロジー

背景:

細胞衰えは細胞循環が不可逆的に停止する状態です
衰老する細胞は組織の老化や病気を促す要因を分泌します
衰老マーカーは神経変性疾患に見られるが,その役割は不明である.

研究の目的:

老化細胞と神経変性との因果関係を調べるためだ
老化細胞を標的にすることで,タウ媒介神経変性病理を予防または治療できるかどうかを判断する.

主な方法:

タウ依存性神経変性疾患のMAPT (P301S) PS19マウスモデルを使用した.
INK-ATTACの変異性マウスを使用し,老化細胞の標的クリアリングを行いました.
グリオシス,タウ高酸化, 神経線維絡の収縮, 神経細胞の喪失, 認知機能の評価

主要な成果:

p16 ((INK4A)) 陽性老化アストロサイトとミクログリアの蓄積が疾患モデルで観察されました.
衰老細胞のクリアランスは,膠着症,タウ病変,神経変異を予防しました.
認知機能は老化細胞クリアランスを持つマウスで維持された.
セノリチス治療はタウの結合を調節した.

結論:

老化細胞は,タウ媒介性神経変性疾患の発症と進行に因果的に寄与する.
老化細胞をターゲットにすることは神経退行性病理に対する潜在的な治療戦略です
衰老の蓄積を防ぐことは,老化や病気で認知機能を保ちます.

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