論文 - 詳細
| RRC ID | 73009 |
|---|---|
| 著者 | Morimoto A, Irie K, Murakami K, Ohigashi H, Shindo M, Nagao M, Shimizu T, Shirasawa T. |
| タイトル | Aggregation and neurotoxicity of mutant amyloid beta (A beta) peptides with proline replacement: importance of turn formation at positions 22 and 23. |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
Aggregation of the amyloid beta peptides (A beta 1-42 and A beta 1-40) plays a pivotal role in pathogenesis of Alzheimer's disease. Although it is widely accepted that the aggregates of A betas mainly consist of beta-sheet structure, the precise aggregation mechanism remains unclear. To identify amino acid residues that are important for the beta-sheet formation, a series of proline-substituted mutants of A beta 1-42 peptides at positions 19-26 was synthesized in a highly pure form and their aggregation ability and neurotoxicity on PC12 cells were investigated. All proline-substituted A beta 1-42 mutants except for 22P- and 23P-A beta 1-42 were hard to aggregate and showed weaker cytotoxicity than wild-type A beta 1-42, suggesting that the residues at positions 19-21 and 24-26 are important for the beta-sheet formation. In contrast, 22P-A beta 1-42 extensively aggregated with stronger cytotoxicity than wild-type A beta 1-42. Since proline has a propensity for beta-turn structure as a Pro-X corner, these data implicate that beta-turn formation at positions 22 and 23 plays a crucial role in the aggregation and neurotoxicity of A beta peptides. |
| 巻・号 | 295(2) |
| ページ | 306-11 |
| 公開日 | 2002-7-12 |
| DOI | 10.1016/s0006-291x(02)00670-8 |
| PII | S0006291X02006708 |
| PMID | 12150948 |
| MeSH | Amino Acid Sequence Amyloid beta-Peptides / chemistry Amyloid beta-Peptides / metabolism Amyloid beta-Peptides / physiology* Animals Chromatography, High Pressure Liquid Molecular Sequence Data PC12 Cells Peptide Fragments / chemistry Peptide Fragments / metabolism Peptide Fragments / physiology* Proline / chemistry* Protein Structure, Secondary Rats Sequence Homology, Amino Acid |
| IF | 2.985 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | PC-12(RCB0009) |