論文 - 詳細
| RRC ID | 37909 |
|---|---|
| 著者 | Kanno T, Tsuchiya A, Tanaka A, Nishizaki T. |
| タイトル | Combination of PKCε Activation and PTP1B Inhibition Effectively Suppresses Aβ-Induced GSK-3β Activation and Tau Phosphorylation. |
| ジャーナル | Mol Neurobiol |
| Abstract |
Glycogen synthase kinase-3β (GSK-3β) is a key element to phosphorylate tau and form neurofibrillary tangles (NFTs) found in tauopathies including Alzheimer's disease (AD). A current topic for AD therapy is focused upon how to prevent tau phosphorylation. In the present study, PKCε activated Akt and inactivated GSK-3β by directly interacting with each protein. Inhibition of protein tyrosine phosphatase 1B (PTP1B), alternatively, caused an enhancement in the tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1), allowing activation of Akt through a pathway along an IRS-1/phosphatidylinositol 3 kinase (PI3K)/3-phosphoinositide-dependent protein kinase-1 (PDK1)/Akt axis, to phosphorylate and inactivate GSK-3β. Combination of PKCε activation and PTP1B inhibition more sufficiently activated Akt and inactivated GSK-3β than each independent treatment, to suppress amyloid β (Aβ)-induced tau phosphorylation and ameliorate spatial learning and memory impairment in 5xFAD transgenic mice, an animal model of AD. This may represent an innovative strategy for AD therapy. |
| 巻・号 | 53(7) |
| ページ | 4787-97 |
| 公開日 | 2016-9-1 |
| DOI | 10.1007/s12035-015-9405-x |
| PII | 10.1007/s12035-015-9405-x |
| PMID | 26328540 |
| MeSH | Amyloid beta-Peptides / toxicity* Animals Enzyme Activation / drug effects Enzyme Activation / physiology Glycogen Synthase Kinase 3 beta / metabolism* Hippocampus / drug effects Hippocampus / metabolism Humans Mice, Transgenic Organ Culture Techniques PC12 Cells Phosphorylation / drug effects Phosphorylation / physiology Protein Kinase C-epsilon / metabolism* Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors* Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism* Rats Rats, Wistar tau Proteins / metabolism* |
| IF | 4.5 |
| 引用数 | 16 |
| WOS 分野 | NEUROSCIENCES |
| 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 | 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 | |
| ヒト・動物細胞 | PC-12(RCB0009) |