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
リソース情報
ヒト・動物細胞 PC-12(RCB0009)