論文 - 詳細
| RRC ID | 81110 |
|---|---|
| 著者 | Nagashima K, Watanabe H, Akasaka T, Ono M. |
| タイトル | Development of Triphenylmethane Dyes for In Vivo Fluorescence Imaging of Aβ Oligomers. |
| ジャーナル | ACS Chem Neurosci |
| Abstract |
Detection of amyloid β (Aβ) oligomers, regarded as the most toxic aggregated forms of Aβ, can contribute to the diagnosis and treatment of Alzheimer's disease (AD). Thus, the development of imaging probes for in vivo visualization of Aβ oligomers is crucial. However, the structural uncertainty regarding Aβ oligomers makes it difficult to design imaging probes with high sensitivity to Aβ oligomers against highly aggregated Aβ fibrils. In this study, we developed Aβ oligomer-selective fluorescent probes based on triphenylmethane dyes through screening of commercially available compounds followed by structure-activity relationship (SAR) studies on cyclic or acyclic 4-dialkylamino groups. We synthesized 11 triarylmethane-based Aβ oligomer probe (TAMAOP) derivatives. In vitro evaluation of fluorescence properties, TAMAOP-9, which had bulky 4-diisobutylamino groups introduced into three benzenes of a twisted triphenylmethane backbone, showed marked fluorescence enhancement in the presence of Aβ oligomers and demonstrated high selectivity for Aβ oligomers against Aβ fibrils. In docking studies using the Aβ trimer model, TAMAOP-9 bound to the hydrophobic surface and interacted with the side chain of Phe20. In vitro section staining revealed that TAMAOP-9 could visualize Aβ oligomers in the brains of AD model mice. An in vivo fluorescence imaging study using TAMAOP-9 showed significantly higher fluorescence signals from the brains of AD model mice than those of age-matched wild-type mice, confirmed by ex vivo section observation. These results suggest that TAMAOP-9 is a promising Aβ oligomer-targeting fluorescent probe applicable to in vivo imaging. |
| 巻・号 | 15(11) |
| ページ | 2233-2242 |
| 公開日 | 2024-6-5 |
| DOI | 10.1021/acschemneuro.4c00053 |
| PMID | 38753435 |
| MeSH | Alzheimer Disease* / diagnostic imaging Alzheimer Disease* / metabolism Amyloid beta-Peptides* / metabolism Animals Brain / diagnostic imaging Brain / metabolism Fluorescent Dyes* / chemistry Humans Methane / analogs & derivatives Methane / chemistry Mice Mice, Transgenic Optical Imaging* / methods Structure-Activity Relationship Trityl Compounds* / chemistry Trityl Compounds* / pharmacology |
| IF | 4.486 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC06344 |