Reference - Detail
| RRC ID | 37909 |
|---|---|
| Author | Kanno T, Tsuchiya A, Tanaka A, Nishizaki T. |
| Title | Combination of PKCε Activation and PTP1B Inhibition Effectively Suppresses Aβ-Induced GSK-3β Activation and Tau Phosphorylation. |
| Journal | 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. |
| Volume | 53(7) |
| Pages | 4787-97 |
| Published | 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 |
| Times Cited | 16 |
| WOS Category | NEUROSCIENCES |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | News |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | PC-12(RCB0009) |