The protective effects of tanshinone IIA on neurotoxicity induced by β-amyloid protein through calpain and the p35/Cdk5 pathway in primary cortical neurons

The characteristic pathological change of Alzheimer’s disease (AD) include deposits of β-amyloid protein (Aβ) in brain, neurofibrillary tangles (NFTs), as well as a few neuronal loss. Evidence shows that Aβ causes calcium influx and induces the cleavage of p35 into p25. Furthermore, the binding of p25 to cyclin-dependent kinase 5 (Cdk5) constitutively activates Cdk5. The p25/Cdk5 complex then hyperphosphorylates tau. Tanshinone IIA (tanIIA), a natural product extracted from Chinese herbal medicine Salvia miltiorrhiza BUNGE, has been reported to exert antioxidative activity. However, its neuroprotective activity remains unclear. The present study determined whether tanIIA protects neurons against Aβ25–35-induced cytotoxicity and detected the association of this protective effect with calpain and the p35/Cdk5 pathway. The results showed that tanIIA protected neurons against the neurotoxicity of Aβ25–35, increased the viability of neurons, decreased expression of phosphorylated tau in neurons induced by Aβ25–35, improved the impairment of the cell ultrastructure (such as nuclear condensation and fragmentation, and neurofibril collapse). Further more, we found that tanIIA maintained the normal expression of p35 on peripheral membranes, and decreased p25 expression in the cytoplasm. TanIIA also inhibited the translocation of Cdk5 from the nucleus into the cytoplasm of primary neurons induced by Aβ25–35. These data suggested that tanIIA possessed neuroprotective action and the protection may involve in calpain and the p35/Cdk5 pathway.

► Tanshinone IIA (tanIIA) is a lipid-soluble compound purified from Danshen.
► β-Amyloid protein (Aβ) induced Alzheimer’s disease like neurodegeneration pathology.
► TanIIA prevented hyperphosphorylated tau and cleavage of p35 into p25 induced by Aβ.
► TanIIA inhibited the translocation of Cdk5 from nucleus into cytoplasm of neurons.
► The protection of tanIIA may involve in calpain and the p35/Cdk5 pathway.