Regulation of extracellular Zn(2+) homeostasis in the hippocampus as a therapeutic target for Alzheimer's disease

Abstract

Introduction: The hippocampus plays an important role in spatial and declarative memory. Zn(2+) is released from glutamatergic (zincergic) neuron terminals in the hippocampus and serves as a signal factor. Synaptic Zn(2+) homeostasis is critical for cognitive activity in the hippocampus. Amyloid-β (Aβ) is a candidate for the pathogenesis of Alzheimer's disease (AD) and interacts with Zn(2+).

Areas covered: This paper gives an overview of the interaction between Aβ and Zn(2+) in the extracellular compartment in the pathophysiology of AD. Aβ is aggregated with Zn(2+) and the aggregation of Aβ-peptides is widely considered to be the critical step in the pathogenesis of AD. The reader will gain an understanding of recent studies on the importance of the interaction of Aβ with Zn(2+) in the pathophysiology and therapeutic strategy of AD. Extracellular Zn(2+) in the hippocampus is a therapeutic target for AD.

Expert opinion: Recent studies show that the inhibition of the interaction of Aβ with extracellular Zn(2+) ameliorates the pathophysiology of AD and that extracellular Zn(2+) in the hippocampus is involved in transiently Aβ-induced cognition deficits. Zn(2+) may play as a key-mediating factor in pathophysiology in which Aβ is involved and is a targeting molecule to prevent the pathogenesis of AD.

Keywords: Alzheimer’s disease; Zn2+ signaling; amyloid-β; hippocampus.