BRAIN and NERVE－神経研究の進歩65巻12号

2013年12月発行

特集 プロテイノパチーの神経病理学

タウオパチーの神経病理学

著者： 吉田眞理¹

所属機関： ¹愛知医科大学加齢医科学研究所

ページ範囲：P.1445 - P.1458

文献概要

はじめに

　神経細胞を含む真核細胞の主要な細胞骨格には，アクチンフィラメント，中間径フィラメント，微小管の3種類がある。細胞骨格は，必要に応じて短時間の間に形成されたり，壊れたりするダイナミックな構造であり，適当な大きさの単位蛋白分子が重合と脱重合を繰り返す。微小管は，α型とβ型のチュブリンが1個ずつ結合したヘテロダイマー（heterodimer）と呼ばれる二量体が重合して形成される。生体内で微小管に結合して，その安定性や形状を制御する役割を果たしているのが微小管結合蛋白（microtubule associated protein：MAP）であり，タウ蛋白質は，分子量約5万のチュブリン結合蛋白（tubulin associated unit：tau）として同定された¹⁾。

　神経細胞の胞体内や軸索内には微小管やニューロフィラメントの網目構造が張り巡らされているが，タウは微小管をつなぐ架橋構造を形成する蛋白の一種である。タウは微小管に結合して重合を促進し，細胞骨格の形成と維持に重要な役割を果たす²⁾。微小管は，胞体内や軸索で細胞小器官や小胞，分子などを運ぶ分子輸送のレールとして働き，タウは軸索輸送のレールである微小管を安定化させる。タウは生理的には可溶性に富み，正常なリン酸化は神経突起伸長や軸索輸送などの微小管の動態を調節している。タウは主として軸索に多く局在するが，細胞体や樹状突起，アストロサイトやオリゴデンドログリアにも存在する^3,4)。最近，タウは神経細胞や非神経細胞の核内にも存在し，酸化ストレスや熱ストレスが神経細胞の核内に非リン酸化タウを誘導することが報告されている⁵⁾。本稿ではタウオパチーの代表的疾患の病理像を概説する。

参考文献

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