Copper Toxicity Links to Pathogenesis of Alzheimer's Disease and Therapeutics Approaches.
Copper Toxicity Links to Pathogenesis of Alzheimer's Disease and Therapeutics Approaches.
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铜毒性与阿尔茨海默氏病和治疗方法的发病机理联系起来。
DOI：
10.3390/ijms21207660
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发表时间：
2020-10-16
影响因子：
5.6
通讯作者：
Lang M
中科院分区：
文献类型：
--
作者：
Ejaz HW;Wang W;Lang M
阿尔茨海默病（Alzheimer's disease，AD）是一种不可逆的、与年龄相关的进行性神经系统疾病，是老年人中最常见的痴呆类型。AD的神经病理学病变是神经纤维缠结（NFT），并且老年斑包括积聚的淀粉样蛋白-β（Aβ），负载有金属离子，包括Cu、Fe或Zn。已有研究表明，金属离子稳态失调是AD的神经毒性因子，其中Cu离子在斑块和可溶性寡聚体的形成中起着重要的阳离子作用，在AD的病理过程中起着重要作用。Cu-Aβ复合物催化活性氧（reactive oxygen species，ROS）的产生，导致氧化损伤。多项研究表明，氧化应激在AD的发病机制中发挥着至关重要的作用。铜水平与AD的关系仍然不明确，因为一些研究表明铜缺乏，而另一些研究表明AD中铜含量较高，因此需要分别增加和降低动物模型中的铜水平，以研究哪一个是原因。二十多年来，许多体外研究致力于确定金属在Aβ积累、氧化损伤和神经毒性中的作用。最后，简要回顾了螯合疗法的现代治疗方法，主要关注铜离子。尽管缺乏强有力的临床优势的证据，迄今为止，推测使用治疗性金属螯合剂是一种有效的策略，AD仍然流行。然而，最近的一些报告，遗传调节铜转运蛋白在AD模型中的治疗这种难治性疾病的启示。这篇综述旨在简要地介绍一个更好地了解铜离子的几个AD功能的现状，并在此提出一些相互矛盾的报告。
Alzheimer’s disease (AD) is an irreversible, age-related progressive neurological disorder, and the most common type of dementia in aged people. Neuropathological lesions of AD are neurofibrillary tangles (NFTs), and senile plaques comprise the accumulated amyloid-beta (Aβ), loaded with metal ions including Cu, Fe, or Zn. Some reports have identified metal dyshomeostasis as a neurotoxic factor of AD, among which Cu ions seem to be a central cationic metal in the formation of plaque and soluble oligomers, and have an essential role in the AD pathology. Cu-Aβ complex catalyzes the generation of reactive oxygen species (ROS) and results in oxidative damage. Several studies have indicated that oxidative stress plays a crucial role in the pathogenesis of AD. The connection of copper levels in AD is still ambiguous, as some researches indicate a Cu deficiency, while others show its higher content in AD, and therefore there is a need to increase and decrease its levels in animal models, respectively, to study which one is the cause. For more than twenty years, many in vitro studies have been devoted to identifying metals’ roles in Aβ accumulation, oxidative damage, and neurotoxicity. Towards the end, a short review of the modern therapeutic approach in chelation therapy, with the main focus on Cu ions, is discussed. Despite the lack of strong proofs of clinical advantage so far, the conjecture that using a therapeutic metal chelator is an effective strategy for AD remains popular. However, some recent reports of genetic-regulating copper transporters in AD models have shed light on treating this refractory disease. This review aims to succinctly present a better understanding of Cu ions’ current status in several AD features, and some conflicting reports are present herein.
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