淫羊藿苷
高磷酸化
神经保护
葛兰素史克-3
神经毒性
τ蛋白
化学
神经退行性变
药理学
细胞生物学
PI3K/AKT/mTOR通路
GSK3B公司
激酶
信号转导
阿尔茨海默病
生物化学
生物
内科学
医学
疾病
毒性
病理
替代医学
有机化学
作者
Ke‐Wu Zeng,Hyeonseok Ko,Hyun Ok Yang,Xuemei Wang
标识
DOI:10.1016/j.neuropharm.2010.07.020
摘要
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.
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