Osthole decreases tau protein phosphorylation via PI3K/AKT/GSK-3β signaling pathway in Alzheimer's disease.

Affiliation

Liaoning University of Traditional Chinese Medicine, Dalian 116600, China. Electronic address: [Email]

Abstract

OBJECTIVE : Alzheimer's disease (AD), a neurodegenerative disease, was characterized by the loss of memory and progressive cognitive deterioration. Up to now, there has no effective drugs to cure or delay the state of illness. Increasing evidence indicates that hyperphosphorylated tau protein plays a pivotal role in the occurrence and development of AD. Therefore, in present study, we aim to investigate whether osthole (OST) could decrease hyperphosphorylated tau protein in AD and the underlying mechanism.
METHODS : The ability of learning and memory was detected by Morris Water Maze. The pathological changes were detected by H&E staining. The percentage of cells apoptosis was detected by TUNEL assay in vivo and Flow Cytometry in intro. The expressions of tau protein and related proteins in PI3K/Akt/GSK-3β signaling pathway were detected by Western Blot.
RESULTS : We found that OST could significantly improve learning and memory dysfunction, ameliorate the histology structure of damaged neural cells in hippocampal area. Moreover, we also found that OST could decrease tau protein phosphorylation as well as inhibit cells apoptosis. To explore the underlying mechanism, we used LY294002 to block PI3K/Akt/GSK-3β signaling pathway, the results from Western bolt showed that the expression of related proteins in PI3K signaling pathway were decreased with LY294002 treated.
CONCLUSIONS : Taken together, the results indicated that OST could decrease phosphorylated tau levels via activation of PI3K/Akt/GSK-3β signaling pathway. Thus, this study demonstrated that OST might be a potential candidate for the treatment of AD.

Keywords

Alzheimer's disease,Apoptosis,Osthole,PI3K,Phosphorylated tau protein,