Synaptic release of Zn2+ activates a Zn2+-sensing receptor, mZnR/GPR39, induces Ca2+-signaling, then activates ERK1/2 MAPK and up-regulates clusterin; however, Zn2+ signaling via mZnR/GPR39 is disrupted by amyloid-β in AD brains, which is a critical pathological component of AD [44]. This evidence concerns the gene MAPK3 and Alzheimer disease.