Amyloid β attenuates metabotropic zinc sensing receptor, mZnR/GPR39, dependent Ca2 , ERK1/2 and Clusterin signaling in neurons

Abstract

A hallmark of Alzheimer's disease is accumulation of amyloid beta (Aβ) deposits, which are associated with neuronal dysfunction, spine loss, and impaired Ca2+ homeostasis. Amyloid beta (Aβ) binds to and is aggregated by Zn2+, a metal released from synaptic glutamatergic vesicles during neuronal activity. Synaptically released Zn2+ activates a metabotropic Gq-coupled Zn2+-sensing receptor, mZnR/GPR39, and induces Ca2+-signaling in post-synaptic neurons. We examined if Aβ, as a Zn2+ binding protein, regulates neuronal Zn2+-signaling mediated by mZnR/GPR39 using SHSY-5Y cells and cortical neurons from GPR39 wild-type and knockout mice. Following acute or chronic treatment with Aβ neuronal Zn2+-..