De Benedictis Chiara A., Vilella Antonietta, Grabrucker Andreas M.
Cellular Neurobiology and Neuro-Nanotechnology Lab, Department of Biological Sciences, University of Limerick, Limerick, Ireland
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
The extracellular aggregation of insoluble protein deposits of amyloid-β (Aβ) into plaques and the hyperphosphorylation of the intracellular protein tau leading to neurofibrillary tangles are the main pathological hallmarks of Alzheimer’s disease (AD). Both Aβ and tau are metal-binding proteins. Essential trace metals such as zinc, copper, and iron play important roles in healthy brain function but altered homeostasis and distribution have been linked to neurodegenerative diseases and aging. In addition, the presence of non-essential trace metals such as aluminum has been associated with AD. Trace metals and abnormal metal metabolism can influence protein aggregation, synaptic signaling pathways, mitochondrial function, oxidative stress levels, and inflammation, ultimately resulting in synapse dysfunction and neuronal loss in the AD brain. Herein we provide an overview of metals and metal-binding proteins and their pathophysiological role in AD.
淀粉样β蛋白（Aβ）不溶性蛋白沉积物在细胞外聚集成斑块，以及细胞内蛋白tau过度磷酸化导致神经原纤维缠结，是阿尔茨海默病（AD）的主要病理标志。Aβ和tau都是金属结合蛋白。锌、铜和铁等必需微量元素在健康大脑功能中发挥重要作用，但内环境稳态和分布的改变与神经退行性疾病及衰老有关。此外，铝等非必需微量元素的存在也与AD相关。微量元素和异常的金属代谢可影响蛋白质聚集、突触信号通路、线粒体功能、氧化应激水平和炎症，最终导致AD大脑中的突触功能障碍和神经元丢失。在此，我们概述了金属和金属结合蛋白及其在AD中的病理生理作用。
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