Icariin attenuates β-amyloid-induced neurotoxicity. - GreenMedInfo Summary
Icariin attenuatesβ-amyloid-induced neurotoxicity by inhibition of tau protein hyperphosphorylation in PC12 cells.
Neuropharmacology. 2010 Nov;59(6):542-50. Epub 2010 Aug 12. PMID: 20708632
Natural Products Research Center, Korea Institute of Science and Technology (KIST) Gangneung Institute, Kangneung 210-340, Republic of Korea.
Alzheimer's disease (AD) is a neurodegenerative disease characterized by the progressive loss of neurons and production ofβ-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 icariinis 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 taupathology-related neuronal degenerative diseases.