Regulation of extracellular Zn²⁺ 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. Zn²⁺ is released from glutamatergic (zincergic) neuron terminals in the hippocampus and serves as a signal factor. Synaptic Zn²⁺ 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 Zn²⁺.

Areas covered: This paper gives an overview of the interaction between Aβ and Zn²⁺ in the extracellular compartment in the pathophysiology of AD. Aβ is aggregated with Zn²⁺ 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 Zn²⁺ in the pathophysiology and therapeutic strategy of AD. Extracellular Zn²⁺ in the hippocampus is a therapeutic target for AD.

Expert opinion: Recent studies show that the inhibition of the interaction of Aβ with extracellular Zn²⁺ ameliorates the pathophysiology of AD and that extracellular Zn²⁺ in the hippocampus is involved in transiently Aβ-induced cognition deficits. Zn²⁺ 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
• amyloid-β
• hippocampus
• Zn²⁺ signaling

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Notes

This box summarizes key points contained in the article.