Tamano Haruna, Takeda Atsushi
Department of Neurophysiology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Metallomics. 2015 Aug;7(8):1205-12. doi: 10.1039/c5mt00076a.
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.
金属离子，即锌离子（Zn(2+)）和铜离子（Cu(2+)），从海马体的神经元末梢释放，海马体在空间记忆和陈述性记忆中起重要作用，且这些金属离子可能作为一种信号因子。金属离子的突触稳态对于海马体的认知活动至关重要。淀粉样β蛋白（Aβ）是阿尔茨海默病（AD）发病机制的致病候选因素，随着正常衰老，Aβ诱导的突触功能障碍容易出现，并导致AD痴呆前期的认知衰退和记忆丧失。由于Aβ与锌离子（Zn(2+)）和铜离子（Cu(2+)）相互作用，这些金属离子很可能参与了Aβ诱导的突触功能改变。有证据表明，抑制Aβ与锌离子（Zn(2+)）和铜离子（Cu(2+)）的相互作用可能改善AD的病理生理过程。海马体中细胞外锌离子（Zn(2+)）与Aβ的相互作用参与了Aβ短暂诱导的认知缺陷，而细胞外铜离子（Cu(2+)）的相互作用降低了细胞内铜离子（Cu(2+)）的生物利用度，随后氧化应激增加，这可能导致认知缺陷。锌离子（Zn(2+)）和铜离子（Cu(2+)）很可能在Aβ参与的突触功能障碍的病理生理过程中作为关键介导因子发挥作用。基于理解Aβ诱导的突触可塑性变化对预防AD很重要这一观点，本文总结了Aβ与金属离子在认知方面的相互作用。
