alpha nu and beta 1 integrins mediate A beta-induced neurotoxicity in primary hippocampal neurons. We treated hippocampal neurons with 2.5 mu g/mL 17E6 and 5 mu g/mL ab58524, which are specific alpha nu and beta 1 integrin antagonists, respectively, for 42 h prior to 10 mu M A beta treatment. Next, we employed small interfering RNA (siRNA) to silence focal adhesion kinase (FAK), a downstream target gene of integrins. The siRNAs were designed with a target sequence, an MOI of 10 and the addition of 5 mu g/mL polybrene. Under these conditions, the neurons were transfected and the apoptosis of different cell types was detected. Moreover, we used real-time PCR and Western blotting analyses to detect the expression of FAK and rho FAK genes in different cell types and investigated the underlying mechanism and signal pathway by which alpha nu and beta 1 integrins mediate A beta-induced neurotoxicity in hippocampal neurons. An MTT assay showed that both 17E6 and ab58524 significantly increased cell viability compared with the A beta-treated neurons (P<0.01 and P<0.05, respectively). However, this protective effect was markedly attenuated after transfection with silencing FAK (siFAK). Moreover, TUNEL immunostaining and flow cytometry indicated that both 17E6 and ab58524 significantly protected hippocampal neurons against apoptosis induced by A beta (P<0.05) compared with the A beta-treated cells. However, this protective effect was reversed with siFAK treatment. Both the gene and protein expression of FAK increased after A beta treatment. Interestingly, as the gene and protein levels of FAK decreased, the rho FAK protein expression markedly increased. Furthermore, both the gene and protein expression of FAK and rho FAK were significantly diminished. Thus, we concluded that both alpha nu and beta 1 integrins interfered with A beta-induced neurotoxicity in hippocampal neurons and that this mechanism partially contributes to the activation of the Integrin-FAK signaling pathway.