Regulation of proapoptotic proteins Bak1 and p53 by miR-125b in an experimental model of Alzheimer's disease: Protective role of 17β-estradiol

•We explored in cortical neurons the miR-125b role in the Aβ peptide neurotoxicity.•Aβ peptide exposure inhibits the axes miR-125b/BAK1 and miR-125b/p53.•The inhibition of miR-125b is a key event in the neurotoxic effect of Aβ peptide.•17β-Estradiol treatment protects from Aβ-induced apoptosis by increasing miR-125b.•miR-125b inhibition abrogates the neuroprotective effect of 17β-estradiol.

Alzheimer's disease has become one of the most impacting disorders since world population is rapidly aging. MicroRNA-125b plays a crucial role in many cellular processes and pathologies, but, to date, its role in Alzheimer's disease is controversial. In this study, we demonstrated, for the first time, that the down regulation of miR-125b is a key event for the neurotoxic effect of Aβ treatment in cortical neurons. Moreover, we found that 17β-estradiol treatment protects neurons from the Aβ-peptide induced neurotoxicity by increasing miR-125b expression that, in turn, decreased the expression, both at gene and protein levels, of the pro-apoptopic proteins Bak1 and p53. Overall, our data reveal miR-125b as a novel neuro-protector miRNA in Alzheimer's disease.