慢性外傷性脳病における新しいタウ線維の折りたたみが,水害性分子を包み込む

Benjamin Falcon¹, Jasenko Zivanov¹, Wenjuan Zhang¹

¹MRC Laboratory of Molecular Biology, Cambridge, UK.

Nature

|March 22, 2019

まとめ

研究者は慢性創傷性脳症 (CTE) のタウ線維の構造を決定した. これらの構造はユニークで CTEの診断と脳内の進行を理解するのに役立ちます

科学分野:

神経科学
生物化学
病理学について

背景:

慢性外傷性脳症 (CTE) は,重複的な頭部衝撃に関連した進行性神経変性タオパシーです.
現在,CTEの診断には解剖が必要で,病気を修正する治療法はありません.
タウ線維の正確な形状とCTEにおけるその形成のメカニズムは不明である.

研究の目的:

CTE患者の脳内の高解像度タウ線維の構造を決定する.
アルツハイマー病などの他の神経変性疾患で見られる CTEのタウ線維構造と比較する.
CTEにおけるタウの集積の構造的基礎を明らかにする.

主な方法:

クリオ電子顕微鏡を用いて,3つのCTE脳からタウ線維を分析した.
構造分析は2. 3 Åまでの解像度で実施された.
既知のタオパシーと比較した構造分析が行われました.

主要な成果:

CTEにおけるタウ・フィラメント構造は3つの症例すべてで同一だったが,アルツハイマー病とピック病とは異なる.
すべての6つの脳タウイソフォームは,CTEでフィラメントに組み合わされ,C形原フィラメントを形成します.
CTEのタウ繊維には独特の防水性穴と独特のプロトフィラメントインターフェースが特定され,コファクターの関与を示唆した.

結論:

決定されたタウ線維構造は,CTEの統合神経病理学的基準を提供します.
この発見は,異なるタウコンフォマーが異なる神経変性疾患の根底にあるという仮説を裏付けている.
これらの構造を理解することで将来のCTEの診断と治療の戦略の基礎が整えるかもしれません

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