Effects of celastrol on Tau hyperphosphorylation and expression of HSF‐1 and HSP70 in SH‐SY5Y neuroblastoma cells induced by amyloid‐β peptides.

Abstract: To observe the effects of celastrol on Tau hyperphosphorylation induced by amyloid‐β peptides (Aβ) in SH‐SY5Y neuroblastoma cells, the changes of Tau hyperphosphorylation and the expression of heat shock protein 90 (HSP90), HSP70, and heat shock factor 1 (HSF‐1) in SH‐SY5Y cells treated with Aβ1–42 and celastrol were measured. Tau hyperphosphorylation and HSP90 expression induced by Aβ1–42 was also measured by Western blotting after HSP70 or HSF‐1 knockdown by siRNA. The interaction between HSP70 and Tau or HSP70 and carboxyl terminus of HSP70 interacting protein (CHIP) was measured by co‐immunoprecipitation. Compared with the control group, the expressions of HSP70 and HSF‐1 were markedly decreased after the induction of Aβ1–42, whereas the expressions of HSP90, Tau phospho S199/202, and Tau phospho S396 were markedly increased. Meanwhile, both celastrol treatment and knockdown of HSP70 or HSF‐1 in SH‐SY5Y cells significantly inhibited the Tau hyperphosphorylation and HSP90 expression induced by Aβ1–42. Moreover, celastrol treatment had no effects on Aβ1–42‐induced decreased expression of HSP70 and HSF‐1, Tau ubiquitination, and the interaction of HSP70/Tau and HSP70/CHIP. These results suggest that celastrol‐inhibited Tau hyperphosphorylation may not be dependent on the cause of HSF‐1/HSP70/CHIP‐mediated ubiquitination of Tau. [ABSTRACT FROM AUTHOR]