Involvement of calpain and p25 of CDK5 pathway in ginsenoside Rb1's attenuation of β-amyloid peptide25-35-induced tau hyperphosphorylation in cortical neurons

Increasing evidence have shown that β-amyloid (Aβ) induced hyperphosphorylation of tau, which eventually resulted in the disruption of microtubule (MT) integrity. Cyclin-dependent kinase 5 (CDK5) and its activator p35 are required for neurite outgrowth. The cleavage of p35 to p25, mediated by calpain and calcium, caused CDK5 dislocation and subsequently p25/CDK5-induced tau hyperphosphorylation, which disrupted the cytoskeleton and resulted in neuronal death. In the present study we investigated the effects of ginsenoside Rb1 on fibrillar Aβ25-35-induced tau hyperphosphorylation in primary cultured cortical neurons and also the potential involvement of Ca2+-calpain-CDK5 signal pathway. The present study suggests that Ca2+, calpain, and p25 in CDK5 pathway may play important roles in Aβ25-35-induced tau hyperphosphorylation.