BRAIN and NERVE－神経研究の進歩61巻3号

2009年03月発行

総説

TRIAD―第3の細胞死

著者： 岡澤均¹

所属機関： ¹東京医科歯科大学神経病理学分野

ページ範囲：P.285 - P.292

文献概要

はじめに

　神経変性疾患の病理学的特徴は，異常蛋白質蓄積と細胞死だといわれる。しかし，近年の分子遺伝学的あるいは分子生物学的な病態解析の結果，細胞死が起きる前から，神経細胞機能障害によって神経変性疾患は発症することが明らかになってきた。この事実は一見，変性病態あるいは変性治療における細胞死の重要性を低下させたように感じさせる。しかし，細胞死は，特に神経細胞死はヒトが長い年月をかけて蓄積してきた情報（海馬ニューロンであれば記憶情報，小脳や脊髄運動ニューロンであれば運動情報）を失うことを意味している。これは，その個人の「人生の記憶」を失うことともいえる。したがって，将来仮に神経再生治療が実用化したとしても，細胞死のダメージは計り知れないものがあり，細胞死の臨床的重要性に変わりはない。

　一方，「細胞死以前の発症」は新たな疑問を提示することになった。つまり，「いかなる細胞機能障害が症状につながるのか？」そして「細胞機能障害がどのように細胞死につながるのか？」という疑問である。本稿では，この2つの疑問についての最近の考え方をレヴューした後に，これらの疑問と密接な関連を持つ新しい細胞死TRIAD（transcriptional repression-induced atypical cell death）の紹介を行いたい。また，TRIADとTDP43-FTDあるいは劣性遺伝ジストニア（DYT3）との関連の可能性についても触れたい。

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