title: Regulation of extracellular Zn(2+) homeostasis in the hippocampus as a therapeutic target for Alzheimer's disease.
abstract: BACKGROUND
  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+).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Shizuoka, School of Pharmaceutical Sciences, Department of Neurophysiology , 52-1 Yada, Suruga-ku, Shizuoka 422-8526 , Japan +81 54 264 5733 ; +81 54 264 5909 ; takedaa@u-shizuoka-ken.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
authors.forename: Haruna
authors.initials: H
authors.lastname: Tamano
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D006624:Hippocampus / Q000473:pathology; D006706:Homeostasis; D006801:Humans; D058990:Molecular Targeted Therapy; D015032:Zinc / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D015032:Zinc
keywords: Alzheimer’s disease; Zn2+ signaling; amyloid-β; hippocampus