title: Is interaction of amyloid β-peptides with metals involved in cognitive activity?
abstract: Metal ions, i.e., Zn(2+) and Cu(2+), are released from neuron terminals in the hippocampus, which plays important roles in spatial and declarative memory, and may serve as a signal factor. Synaptic homeostasis of metal ions is critical for cognitive activity in the hippocampus. Amyloid-β (Aβ) is a causative candidate for the pathogenesis of Alzheimer's disease (AD) and Aβ-induced synapse dysfunction is easy to emerge along with normal aging and leads to the cognitive decline and memory loss in the pre-dementia stage of AD. Because Aβ interacts with Zn(2+) and Cu(2+), it is likely that these metal ions are involved in the Aβ-induced modification of the synaptic function. There is evidence to indicate that the inhibition of the interaction of Aβ with Zn(2+) and Cu(2+) may ameliorate the pathophysiology of AD. Interaction of extracellular Zn(2+) with Aβ in the hippocampus is involved in transiently Aβ-induced cognition deficits, while the interaction of extracellular Cu(2+) reduces bioavailability of intracellular Cu(2+), followed by an increase in oxidative stress, which may lead to cognitive deficits. It is likely that Zn(2+) and Cu(2+) play as a key-mediating factor in pathophysiology of the synaptic dysfunction in which Aβ is involved. Based on the idea that understating Aβ-induced changes in synaptic plasticity is important to prevent AD, the present paper summarizes the interaction of Aβ with metal ions in cognition.
authors.affiliation: Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. takedaa@u-shizuoka-ken.ac.jp.
authors.forename: Haruna
authors.initials: H
authors.lastname: Tamano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002413:Cations, Divalent / Q000378:metabolism; D003071:Cognition; D003300:Copper / Q000378:metabolism*; D006801:Humans; D009473:Neuronal Plasticity; D066263:Protein Aggregation, Pathological / Q000378:metabolism / Q000473:pathology; D013569:Synapses / Q000378:metabolism / Q000473:pathology; D015032:Zinc / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D002413:Cations, Divalent; D003300:Copper; D015032:Zinc