著者

齊ノ内 信 中村 道三 増田 裕一 大谷 良

出版者

日本神経学会

雑誌

臨床神経学 (ISSN:0009918X)

巻号頁・発行日

pp.cn-001489, (Released:2020-12-15)

参考文献数

20

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症例は86歳女性.調理中に突然出現した複視を主訴に来院した.両眼性複視,両側眼球内転障害と輻湊障害,両側側方注視時に外転眼のみに粗大な単眼性眼振を認めた.入院翌日のMRIで中脳下部背側に拡散低下域を認めた.入院1日半後に尿閉,尿意の消失に気付かれた.脳梗塞を念頭に抗血小板薬で治療を行い,発症2ヶ月後には眼球運動は正常になり,複視も消失.尿閉も消失した.眼球運動障害については動眼神経の内転筋亜核から両側medial longitudinal fasciculusにかけての病変を想定している.尿閉については排尿中枢の一つである中脳水道周囲灰白質への障害が原因と考えている.中脳の微小な梗塞で尿閉を呈する例は稀であるため報告する.

著者

入江 一浩 増田 裕一 村上 一馬 上村 諭子 大東 肇 原 英之 大橋 竜太郎 中西 梓 竹腰 清乃理

出版者

天然有機化合物討論会

雑誌

天然有機化合物討論会講演要旨集

巻号頁・発行日

no.49, pp.61-66, 2007-08-24

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Aggregation of the 42-mer amyloid β (Aβ42) plays a central role in the pathogenesis of Alzheimer's disease. Our recent research on the systematic replacement of Aβ42 with proline suggested that the formation of a turn structure at Glu-22 and Asp-23 could be essential to the potent aggregative ability and neurotoxicity of Aβ42. We verified the existence of this turn structure in the minor conformer of wild-type Aβ42 and E22K-Aβ42 (Italian mutation), by solid-state NMR using dipolar assisted rotational resonance (DARR). In E22K-Aβ42, the ionic interaction between Lys-22 and Asp-23 might promote the turn formation at this site. In order to identify the toxic conformation of Aβ42, we synthesized Aβ42-lactam(22K-23E) as a conformationally restricted analogue of the minor conformer, whose side chains of Lys-22 and Glu-23 are linked with an amide bond. Aβ42-lactam(22K-23E) showed much stronger aggregative ability and neurotoxicity than E22K-Aβ42. This implies that the minor conformer with a turn at Glu-22 and Asp-23 of Aβ42 should be considered as a toxic form. Neurotoxicity of Aβ42 is closely related to the radicalization at both Tyr-10 and Met-35. Our previous study reminds us that the S-oxidized radical cation at position 35, the ultimate toxic radical species, would be produced effectively through oxidation by the phenoxy radical at position 10 in the toxic conformer. Electron spin resonance (ESR) spectrometry using spin-labeling with MTSSL revealed that these residues are close to each other in Aβ42. This finding clearly accounts for the reason why the toxic conformer is more pathogenic than the physiological one.