effects of amyloid precursor protein overexpression on nf-κb, rho-gtpase and pro-apoptosis bcl-2 pathways in neuronal cells

Background: alzheimer’s disease (ad) is a neurodegenerative disorder that causes cognitive dysfunction. previous studies have suggested that amyloid plaques, mainly comprising of amyloid-beta peptides, play a pivotal role in ad pathophysiology. this study focuses on the evaluation of the effects of amyloid precursor protein (app) overexpression on nf-κb, rho-gtpase and bcl-2 mediated pro-apoptotic pathways in neuronal cells.methods: a lentiviral transduction system was used to generate sh-sy5y cells overexpressing app. immunoblotting was conducted to determine expression levels of nf-κb, rho-gtpase, and bcl-2 family proteins in the app overexpressed cells.results: in the nf-κb signaling pathway, app-overexpressing sh-sy5y cells showed that there was a reduction of p-nf-κb (p< 0.05) and ikkα. subsequently, there was upregulation of protein expression of nf-κb, ikkβ and iκbα. on the other hand, protein expression of rhoc (p< 0.05) and rac1/2/3 was upregulated as compared to the control group. meanwhile, a decrease in rhoa, cdc42 (p< 0.05) and p-rac1/cdc42 protein levels was observed in the app-overexpressed group. lastly, in the pro-apoptotic pathway, the expression of bcl-2, bid, bok and puma (p< 0.05) was up regulated in the app-overexpressed group. downregulation of bad and bim expression was observed in the app-overexpressed as compared to the control group, and bax expression remained unchanged in the app-overexpressed group.conclusions: app overexpression regulated signaling in the nf-κb, rho-gtpase and bcl-2 family pathways in neuronal cells, suggesting that these are involved in promoting neuronal survival and modulating synaptic plasticity in ad. however, further studies are essential to elucidate the app-mediated mechanism of action.