BRAIN and NERVE－神経研究の進歩61巻2号

2009年02月発行

総説

TDP-43と神経変性疾患

著者： 野中隆¹ 犬飼有紀¹ 新井哲明² 長谷川成人¹

所属機関： ¹東京都精神医学総合研究所分子神経生物学研究チーム ²東京都老年期精神疾患研究チーム

ページ範囲：P.161 - P.166

文献概要

はじめに

　2006年，筆者ら^1，2）およびNeumannら^3）のグループは，前頭側頭葉変性症（frontotemporal lobar degeneration: FTLD）および筋萎縮性側索硬化症（amyotrophic lateral sclerosis: ALS）患者脳に認められるユビキチン陽性細胞内凝集体（封入体）の主要構成蛋白質として，TAR DNA-binding protein of 43 kDa（TDP-43）を同定した。2008年，家族性および孤発性ALSの患者に，TDP-43遺伝子変異が相次いで発見され^4－11），FTLDおよびALSの発症とTDP-43の異常が直接関連することが判明した。現在TDP-43は，タウ，αシヌクレインに次いで，神経変性疾患に出現する封入体を構成する第3の主要な蛋白質として注目を集めている。本稿では，TDP-43に関する最新の知見を筆者らの研究成果とともに紹介し，FTLDやALSの発症メカニズムとTDP-43の異常との関連性について考察したい。

参考文献

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