P-28 アミロイドβ(Aβ42)の毒性コンホマー特異的抗体の作製(ポスター発表の部)

• 村上 一馬

  京大院農

• 増田 裕一

  京大院農

• 入江 一浩

  京大院農

• 堀越(櫻庭) 優子

  免疫生物研究所

• 木下 憲明

  免疫生物研究所

• 村田 央

  都健康長寿医療セ

• 野田 義博

  都健康長寿医療セ

• 初田 裕幸

  都健康長寿医療セ

• 村山 繁雄

  都健康長寿医療セ

• 白澤 卓二

  都健康長寿医療セ

• 清水 孝彦

  都健康長寿医療セ

書誌事項

タイトル別名

• Development of Monoclonal Antibody Against the Toxic Conformer of Amyloid β Peptide (Aβ42)

抄録

Aggregation of the 42-mer amloid β proptide (Aβ42) plays a pirotal role in the pathogenesis of Alzheimer's disease (AD). Aβ42 is physiologically produced from amyloid precursor protein by two proteases, while Aβ42 aggregates to form the toxic oligomer causing the cognitive impairment and synaptic loss in the presence of metals, oxidative stress, and abnormal lipid proteins. Although the imunotherapy targeting Aβ42 affrefates has been proved useful, the clinical trials are conductiong with caution because of severe adverse effects in some cases. We hypothesize these adverse effets could be due to excessive immunoreactions derived from the unintended removal of physiological Aβ42. Our recent studies of solid-state NMR and systematic proline replacement showed a toxic conformer of Aβ42 with a turn at Glu22 and Asp23 as well as a non-toxic one with a turn at positions Gly25 and Ser26 (Fig. 1). Here we report a monoclonal antibody ofr the toxic Aβ42, in which E22P-Aβ10-35, a minimum moiety for neurotoxocity including the toxic turn at Glu22 and Asp23, was used as a hapten (Fig. 1). The selected clone (11A1) inhibited the neurotoxocity of Aβ42 and E22P-Aβ42 on PC12 cells estimated by MTT assay (Fig. 4). Immunohistochemical studies showed that not only extracellular but intracellular amyloid was stained in the brains of AD patients (Fig. 5). 11A1 recognized oligomers rather than the monomer of Aβ in Western blots using human AD tissues (Fig. 6). These results suggest that 11A1 can detect Aβ42 assembles containing the toxic turn at Glu22 and Asp23 within cells. 11A1 might be applicable to anti-Aβ therapeutic approaches.

収録刊行物

• 天然有機化合物討論会講演要旨集

  天然有機化合物討論会講演要旨集 52 (0), 553-558, 2010

  天然有機化合物討論会実行委員会

詳細情報

• CRID: 1390282681054175488
• NII論文ID: 110009757817
• DOI: 10.24496/tennenyuki.52.0_553
• ISSN: 24331856
• 本文言語コード: ja
• データソース種別:
  • JaLC
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可