Reference - Detail
| RRC ID | 73009 |
|---|---|
| Author | Morimoto A, Irie K, Murakami K, Ohigashi H, Shindo M, Nagao M, Shimizu T, Shirasawa T. |
| Title | Aggregation and neurotoxicity of mutant amyloid beta (A beta) peptides with proline replacement: importance of turn formation at positions 22 and 23. |
| Journal | 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. |
| Volume | 295(2) |
| Pages | 306-11 |
| Published | 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 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 6 |
| Altmetric score changes over past 6months | 3.0 |
| Resource | |
| Human and Animal Cells | PC-12(RCB0009) |