APP and Alzheimer disease: Based on previous results showing that melatonin alleviates AD through enhanced nonamyloidogenic processing of APP and ADAM10 expression via activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway,30 we examined whether MAPK/ERK activation also mediates the effect of melatonin on PIAS1 expression.