| 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
|
| Resource |
| Human and Animal Cells |
PC-12(RCB0009) |
