Genistein protects against amyloid-beta-induced toxicity in SH-SY5Y cells by regulation of Akt and Tau phosphorylation.

Alzheimer's disease is a neurodegenerative disorder characterized by extracellular deposition of amyloid-beta (A beta) peptide and hyperphosphorylation of Tau protein, which ultimately leads to the formation of intracellular neurofibrillary tangles and cell death. Increasing evidence indicates that genistein, a soy isoflavone, has neuroprotective effects against A beta-induced toxicity. However, the molecular mechanisms involved in its neuroprotection are not well understood. In this study, we have established a neuronal damage model using retinoic-acid differentiated SH-SY5Y cells treated with different concentrations of A beta(25-35) to investigate the effect of genistein against A beta-induced cell death and the possible involvement of protein kinase B (PKB, also termed Akt), glycogen synthase kinase 3 beta (GSK-3 beta), and Tau as an underlying mechanism to this neuroprotection. Differentiated SH-SY5Y cells were pre-treated for 24 hr with genistein (1 and 10 nM) and exposed to A beta(25-35) (25 mu M), and we found that genistein partially inhibited A beta induced cell death, primarily apoptosis. Furthermore, the protective effect of genistein was associated with the inhibition of A beta-induced Akt inactivation and Tau hyperphosphorylation. These findings reinforce the neuroprotective effects of genistein against A beta toxicity and provide evidence that its mechanism may involve regulation of Akt and Tau proteins.