Glia and zinc in ageing and Alzheimer's disease: a mechanism for cognitive decline?
Glia and zinc in ageing and Alzheimer's disease: a mechanism for cognitive decline?
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DOI：
10.3389/fnagi.2014.00137
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发表时间：
2014
影响因子：
4.8
通讯作者：
Adlard PA
中科院分区：
文献类型：
--
作者：
Hancock SM;Finkelstein DI;Adlard PA
正常衰老的特点是一系列神经功能的认知能力下降，在阿尔茨海默病(AD)中会进一步受损。最近，锌浓度的变化，特别是突触的锌浓度的变化，已经成为衰老和阿尔茨海默病认知变化的潜在机制。锌现在被认为是一种强有力的神经调节剂，影响突触上对正常认知至关重要的各种信号通路。虽然研究的重点主要集中在神经元与锌的相互作用上，但越来越多的文献表明，胶质细胞也可能在维持锌离子稳态和突触的正常功能方面发挥调节作用。事实上，锌转运蛋白(ZNT)已经在神经胶质细胞中被证明，锌也被证明在信号转导中起作用。此外，越来越多的证据表明，阿尔茨海默病的发病机制与胶质细胞(如星形胶质细胞)密切相关，据报道，胶质细胞与淀粉样β蛋白(Aβ)神经毒性有关。这篇综述讨论了目前支持神经胶质细胞、锌代谢紊乱和突触功能在衰老和阿尔茨海默病中复杂相互作用的证据。
Normal ageing is characterized by cognitive decline across a range of neurological functions, which are further impaired in Alzheimer’s disease (AD). Recently, alterations in zinc (Zn) concentrations, particularly at the synapse, have emerged as a potential mechanism underlying the cognitive changes that occur in both ageing and AD. Zn is now accepted as a potent neuromodulator, affecting a variety of signaling pathways at the synapse that are critical to normal cognition. While the focus has principally been on the neuron: Zn interaction, there is a growing literature suggesting that glia may also play a modulatory role in maintaining both Zn ion homeostasis and the normal function of the synapse. Indeed, zinc transporters (ZnT’s) have been demonstrated in glial cells where Zn has also been shown to have a role in signaling. Furthermore, there is increasing evidence that the pathogenesis of AD critically involves glial cells (such as astrocytes), which have been reported to contribute to amyloid-beta (Aβ) neurotoxicity. This review discusses the current evidence supporting a complex interplay of glia, Zn dyshomeostasis and synaptic function in ageing and AD.
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