Carboxyl-terminus of the amyloid protein precursor and ERbeta are required for estrogenic effect in activating mitogen-activated protein kinase.

Estrogen influences the processing of the amyloid beta precursor protein (APP) in the pathogenesis of Alzheimer's disease, and this effect is mediated by estrogen receptors (ERs) in activating mitogen-activated protein kinase (MAPK)-signaling pathway. To test whether the estrogenic effect on both carboxyl-terminal amino acid fragment (C-terminal) of APP (APP-C105)- and ERbeta-mediated MAPK activation in in vitro, two hybrid genes containing each human ERbeta and APP-C105 gene fused to the neuron-specific enolase (NSE) promoter were constructed and were transfected to the neuronal SK-N-MC cells. Western blot shows that the activation of JNK-signaling pathway, but not p38 and ERK, is dependent on ERbeta through estrogen treatment and APP-C105 is also mediated through estrogen in activating MAPK-signaling pathway. The results suggest that ERbeta and APP-C105 derived from APP are necessary for estrogenic effect in activating MAPK-signaling pathway.