論文 - 詳細
| RRC ID | 45424 |
|---|---|
| 著者 | Takasugi N, Sasaki T, Shinohara M, Iwatsubo T, Tomita T. |
| タイトル | Synthetic ceramide analogues increase amyloid-β 42 production by modulating γ-secretase activity. |
| ジャーナル | Biochem Biophys Res Commun |
| Abstract |
γ-Secretase cleaves amyloid β-precursor protein (APP) to generate amyloid-β peptide (Aβ), which is a causative molecule of Alzheimer disease (AD). The C-terminal length of Aβ, which is determined by γ-secretase activity, determines the aggregation and deposition profiles of Aβ, thereby affecting the onset of AD. In this study, we found that the synthetic ceramide analogues dl-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) and (1S,2R-d-erythro-2-N-myristoylamino)-1-phenyl-1-propanol (DMAPP) modulated γ-secretase-mediated cleavage to increase Aβ42 production. Unexpectedly, PDMP and DMAPP upregulated Aβ42 production independent of alteration of ceramide metabolism. Our results propose that synthetic ceramide analogues function as novel γ-secretase modulators that increase Aβ42, and this finding might lead to the understanding of the effect of the lipid environment on γ-secretase activity. |
| 巻・号 | 457(2) |
| ページ | 194-9 |
| 公開日 | 2015-2-6 |
| DOI | 10.1016/j.bbrc.2014.12.087 |
| PII | S0006-291X(14)02276-1 |
| PMID | 25545059 |
| MeSH | Amyloid Precursor Protein Secretases / metabolism* Amyloid beta-Peptides / biosynthesis* Animals Apoptosis / drug effects Benzyl Alcohols / chemistry Benzyl Alcohols / pharmacology* CHO Cells Ceramides / chemistry* Cricetinae Cricetulus HEK293 Cells Humans Mice Morpholines / chemistry* Morpholines / pharmacology Mutation / genetics Peptide Fragments / biosynthesis* Up-Regulation / drug effects |
| IF | 2.985 |
| 引用数 | 10 |
| WOS 分野 | BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 2 |
| 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 | |
| ヒト・動物細胞 | GM95(RCB1026) MEB4(RCB1027) |