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

αシヌクレイン病変のはじまりとひろがり―パーキンソン病を中心に

著者： 内原俊記¹

所属機関： ¹東京都医学総合研究所脳病理形態研究室

ページ範囲：P.1459 - P.1475

文献概要

はじめに

　シナプスに豊富に存在するαシヌクレインは神経細胞に沈着し，パーキンソン病やレヴィ小体型認知症に特徴的なレヴィ小体（Lewy body）を形成する。疾患関連蛋白がこうして特徴的病変をつくる過程と細胞死の関連を中心にプロテイノパチーの概念は展開されてきた。しかし同様にαシヌクレインが沈着する多系統萎縮症（multiple system atrophy：MSA）の病態はパーキンソン病とは異なり，疾患関連蛋白から両者の病態を区別するのは困難である。

　本稿では細胞体のレヴィ小体形成に先行して起こる軸索末端（前終末）の機能，形態の早期変化がパーキンソン病を特徴づける病態であることに注目する。レヴィ小体が好発する神経細胞は分岐の豊富な長い軸索を持つという背景構造が共通しており，その遠位末端になるほど及ぶ影響がいっそう強調される。シナプス機能の脱落，軸索内のαシヌクレイン沈着が相互に関連しながらパーキンソン病早期に起こり，臨床症状の発現につながることが推測される。関与する神経伝達物質は異なっても，豊富な軸索分岐に対応する系が障害されるパーキンソン病の臨床症状は局在性に乏しく，影響も全体的な点で共通する。この病態を念頭にシナプス前終末の早期変化を捉えて診断できれば，細胞死が起こる前の治療介入も可能になる。

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