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

: 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.