Salidroside reduces tau hyperphosphorylation via up-regulating GSK-3β phosphorylation in a tau transgenic Drosophila model of Alzheimer's disease

Background: Alzheimer's disease (AD) is an age-related and progressive neurodegenerative disease that causes substantial public health care burdens. Intensive efforts have been made to find effective and safe treatment against AD. Salidroside (Sal) is the main effective component of Rhodiola rosea L., which has several pharmacological activities. The objective of this study was to investigate the efficacy of Sal in the treatment of AD transgenic Drosophila and the associated mechanisms. Methods: We used tau transgenic Drosophila line (TAU) in which tau protein is expressed in the central nervous system and eyes by the Gal4/UAS system. After feeding flies with Sal, the lifespan and locomotor activity were recorded. We further examined the appearance of vacuoles in the mushroom body using immunohistochemistry, and detected the levels of total glycogen synthase kinase 3 beta (t-GSK-3 beta), phosphorylated GSK-3 beta (p-GSK-3 beta), t-tau and p-tau in the brain by western blot analysis. Results: Our results showed that the longevity was improved in salidroside-fed Drosophila groups as well as the locomotor activity. We also observed less vacuoles in the mushroom body, upregulated level of p-GSK-3 beta and downregulated p-tau following Sal treatment. Conclusion: Our data presented the evidence that Sal was capable of reducing the neurodegeneration in tau transgenic Drosophila and inhibiting neuronal loss. The neuroprotective effects of Sal were associated with its up-regulation of the p-GSK-3 beta and down-regulation of the p-tau.