Insight into Glutamate Excitotoxicity from Synaptic Zinc Homeostasis

Abstract

Zinc is released from glutamatergic (zincergic) neuron terminals in the hippocampus, followed by the increase in Zn2+concentration in the intracellular (cytosol) compartment, as well as that in the extracellular compartment. The increase in Zn2+concentration in the intracellular compartment during synaptic excitation is mainly due to Zn2+influx through calcium-permeable channels and serves as Zn2+signaling as well as the case in the extracellular compartment. Synaptic Zn2+homeostasis is important for glutamate signaling and altered under numerous pathological processes such as Alzheimer's disease. Synaptic Zn2+homeostasis might be altered in old age, and this alteration might be involved in the pathogenesis and progression of Alzheimer's disease; Zinc may play as a key-mediating factor in the pathophysiology of Alzheimer's disease. This paper summarizes the role of Zn2+signaling in glutamate excitotoxicity, which is involved in Alzheimer's disease, to understand the significance of synaptic Zn2+homeostasis in the pathophysiology of Alzheimer's disease.