The hyperphosphorylation of the
protein tau disrupts its normal function on regulating axonal transport and leads to the accumulation of neurofibrillary tangles (NFT), which are involved in the pathogenesis of
Alzheimer's disease (AD). This study was performed to investigate whether
sodium selenite may inhibit the hyperphosphorylation of tau induced by treatment with
tumor necrosis factor‑α (TNF‑α). For this purpose, we studied the changes in cell viability, tau phosphorylation and activity of tau
kinases in TNF‑α+selenite-treated
neuroblastoma cells. Cell viability was significantly recovered in the group cotreated with TNF‑α and 5 µM
selenite for 24 h, but not in the groups treated with TNF‑α and lower concentrations of
selenite. Tau phosphorylation was significantly higher in the group treated with TNF‑α+vehicle (instead of
selenite) compared to the non‑treated group. However, in the TNF‑α+selenite‑treated group, the total phosphorylation level of
tau protein at the Ser404 site was significantly reduced compared to the TNF‑α+vehicle group, although western blot analysis revealed one band of increased intensity in the p‑tau sample, corresponding to a phosphorylated tau
isoform of 65‑70 kDa. In addition,
sodium selenite treatment led to a significant recovery in the immunofluorescence intensity of the p‑tau
protein in the cytoplasm and nucleus and in the apoptotic rate of
neuroblastoma cells stained with the p‑tau antibody and 4',6‑diamidino‑2‑phenylindole (
DAPI). The phosphorylation of two
protein kinases responsible for phosphorylation of tau,
glycogen synthase kinase 3β (GSK‑3β) and Akt, also known as
protein kinase B, was markedly decreased in the TNF‑α+selenite‑treated group relative to the TNF‑α+vehicle‑treated group. Overall, these results provide strong evidence that
sodium selenite (
selenium) can inhibit cell death and tau phosphorylation induced by TNF‑α in
neuroblastoma cells, through the inhibition GSK‑3β and Akt phosphorylation.