RRC ID 19164
Author Zeng KW, Ko H, Yang HO, Wang XM.
Title Icariin attenuates β-amyloid-induced neurotoxicity by inhibition of tau protein hyperphosphorylation in PC12 cells.
Journal Neuropharmacology
Abstract Alzheimer's disease (AD) is a neurodegenerative disease characterized by the progressive loss of neurons and production of β-amyloid proteins (Aβ). Hyperphosphorylation of tau protein is proposed to be an early event for the evolution of AD, and may play an important role in Aβ-induced neurodegeneration. Icariin, a flavonoid compound from the herb Epimedium brevicornum Maxim, exerts a protective effect on learning and memory abilities in Aβ(25-35)-induced AD rats. However, the molecular mechanism of icariin-induced neuroprotective effect against tau protein hyperphosphorylation, which is one of the most representative hallmarks in AD, is still unknown. In the present study, we investigated the inhibitory effect of icariin on Aβ(25-35)-induced tau protein hyperphosphorylation on PC12 cells. The results showed that treatment with icariin significantly decreased Aβ(25-35)-induced cytotoxicity and apoptosis rate through inhibiting tau protein hyperphosphorylation at Ser396, Ser404 and Thr205 sites, respectively. Mechanism study showed that icariin could activate PI3K/Akt signaling pathway, resulting in an inhibitory effect on glycogen synthase kinase (GSK)-3β, which is an important kinase response for tau protein hyperphosphorylation in the development of AD. These observations indicate that icariin is capable of attenuating Aβ(25-35)-induced tau protein hyperphosphorylation and promoting survival of neuronal cells, meanwhile also provide some insights into the potential signaling pathway that is involved. Thus, this study promises a great potential agent for Alzheimer's disease and other tau pathology-related neuronal degenerative diseases.
Volume 59(6)
Pages 542-50
Published 2010-11
DOI 10.1016/j.neuropharm.2010.07.020
PII S0028-3908(10)00189-9
PMID 20708632
MeSH Amyloid beta-Peptides / metabolism Amyloid beta-Peptides / pharmacology* Analysis of Variance Animals Apoptosis / drug effects Blotting, Western Cell Survival / drug effects Flavonoids / pharmacology* Fluorescent Antibody Technique Neurons / drug effects* Neurons / metabolism PC12 Cells Peptide Fragments / metabolism Peptide Fragments / pharmacology* Phosphorylation / drug effects* Rats tau Proteins / metabolism*
IF 4.249
Times Cited 46
WOS Category PHARMACOLOGY & PHARMACY NEUROSCIENCES
Resource
Human and Animal Cells PC-12 (RCB0009)