In summary, this study found that PIAS3 increased cell survival and antioxidant response and prevented apoptosis of Aβ-treated SH-SY5Y cells via regulating STAT3/Nestin/Nrf2/HO-1 signal pathway.Based on these data, it may be hypothesized that PIAS3/STAT3 and Nestin/Nrf2/HO-1 crosstalk occurs in patients with AD. This evidence concerns the gene HMOX1 and Alzheimer disease.