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Characterization of a Conformation-Restricted Amyloid β Peptide and Immunoreactivity of Its Antibody in Human AD brain.
http://hdl.handle.net/10422/00013090
http://hdl.handle.net/10422/00013090a1a29637-3b8c-429d-988d-cf4c30e75135
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
acschemneuro.1c00416 (12.0 MB)
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https://creativecommons.org/licenses/by-nc-nd/4.0/
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-10-04 | |||||
| タイトル | ||||||
| タイトル | Characterization of a Conformation-Restricted Amyloid β Peptide and Immunoreactivity of Its Antibody in Human AD brain. | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | THP- | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Aβ oligomer | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | protofibril | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Aβ fibril | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Aβ toxic conformer | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Alzheimer’s disease | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| 著者 |
KAGEYAMA, Yusuke
× KAGEYAMA, Yusuke× IRIE, Yumi× MATSUSHIMA, Yuka× SEGAWA, Tatsuya× BELLIER, Jean-Pierre× HIDAKA, Kumi× SUGIYAMA, Hiroshi× KANEDA, Daita× HASHIZUME, Yoshio× AKATSU, Hiroyasu× MIKI, Kunio× KITA, Akiko× WALKER, Douglas Gordon× IRIE, Kazuhiro× TOOYAMA, Ikuo |
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| 著者別名 |
景山, 裕介
× 景山, 裕介× 遠山, 育夫 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Characterization of amyloid β (Aβ) oligomers, the transition species present prior to the formation of Aβ fibrils and that have cytotoxicity, has become one of the major topics in the investigations of Alzheimer's disease (AD) pathogenesis. However, studying pathophysiological properties of Aβ oligomers is challenging due to the instability of these protein complexes in vitro. Here, we report that conformation-restricted Aβ42 with an intramolecular disulfide bond at positions 17 and 28 (SS-Aβ42) formed stable Aβ oligomers in vitro. Thioflavin T binding assays, nondenaturing gel electrophoresis, and morphological analyses revealed that SS-Aβ42 maintained oligomeric structure, whereas wild-type Aβ42 and the highly aggregative Aβ42 mutant with E22P substitution (E22P-Aβ42) formed Aβ fibrils. In agreement with these observations, SS-Aβ42 was more cytotoxic compared to the wild-type and E22P-Aβ42 in cell cultures. Furthermore, we developed a monoclonal antibody, designated TxCo-1, using the toxic conformation of SS-Aβ42 as immunogen. X-ray crystallography of the TxCo-1/SS-Aβ42 complex, enzyme immunoassay, and immunohistochemical studies confirmed the recognition site and specificity of TxCo-1 to SS-Aβ42. Immunohistochemistry with TxCo-1 antibody identified structures resembling senile plaques and vascular Aβ in brain samples of AD subjects. However, TxCo-1 immunoreactivity did not colocalize extensively with Aβ plaques identified with conventional Aβ antibodies. Together, these findings indicate that Aβ with a turn at positions 22 and 23, which is prone to form Aβ oligomers, could show strong cytotoxicity and accumulated in brains of AD subjects. The SS-Aβ42 and TxCo-1 antibody should facilitate understanding of the pathological role of Aβ with toxic conformation in AD. | |||||
| 書誌情報 |
en : ACS chemical neuroscience 巻 12, 号 18, p. 3418-3432, 発行日 2021-09-15 |
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| 出版者 | ||||||
| 出版者 | American Chemical Society | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1948-7193 | |||||
| PMID | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 34464082 | |||||
| DOI | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1021/acschemneuro.1c00416 | |||||
| 関連名称 | 10.1021/acschemneuro.1c00416 | |||||
| 権利 | ||||||
| 権利情報 | © 2021, American Chemical Society | |||||
| フォーマット | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | ||||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| 資源タイプ | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Journal Article | |||||
