PDF(Pubmed)
Abstract：
Zinc (Zn) and copper (Cu) are essential for normal brain functions. In particular, Zn and Cu are released to synaptic clefts during neuronal excitation. Synaptic Zn and Cu regulate neuronal excitability, maintain calcium (Ca) homeostasis, and play central roles in memory formation. However, in pathological conditions such as transient global ischemia, excess Zn is secreted to synaptic clefts, which causes neuronal death and can eventually trigger the pathogenesis of a vascular type of senile dementia. We have previously investigated the characteristics of Zn-induced neurotoxicity and have demonstrated that low concentrations of Cu can exacerbate Zn neurotoxicity. Furthermore, during our pharmacological approaches to clarify the molecular pathways of Cu-enhanced Zn-induced neurotoxicity, we have revealed the involvement of Ca homeostasis disruption. In the present review, we discuss the roles of Zn and Cu in the synapse, as well as the crosstalk between Zn, Cu, and Ca, which our study along with other recent studies suggest may underlie the pathogenesis of vascular-type senile dementia.
摘要：
锌（Zn）和铜（Cu）对于正常的大脑功能至关重要。特别是,Zn和Cu在神经元兴奋期间释放到突触裂隙。突触锌和铜调节神经元兴奋性，维持钙（Ca）稳态，并在记忆形成中发挥核心作用。然而,在短暂的全脑缺血等病理条件下，过量的锌被分泌到突触间隙，导致神经元死亡，并最终引发血管性老年性痴呆的发病机制。我们先前已经研究了锌诱导的神经毒性的特征，并证明低浓度的铜可以加剧锌的神经毒性。此外，在我们的药理学方法来阐明铜增强锌诱导的神经毒性的分子途径，我们已经揭示了Ca稳态破坏的参与。在本次审查中，我们讨论了Zn和Cu在突触中的作用，以及Zn之间的串扰，Cu,Ca,我们的研究以及其他最近的研究表明，这可能是血管性老年性痴呆的发病机理的基础。
