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生物金属作为阿尔茨海默病神经退行性衰退的潜在预测指标

Biometals as Potential Predictors of the Neurodegenerative Decline in Alzheimer's Disease.

作者信息

Lavado Liseth K, Zhang Michelle H, Patel Karan, Khan Sohim, Patel Urvish K

机构信息

Nursing, Rutgers School of Nursing, Newark, USA.

Psychological & Brain Sciences and Biology, Johns Hopkins University, Baltimore, USA.

出版信息

Cureus. 2019 Sep 5;11(9):e5573. doi: 10.7759/cureus.5573.

Abstract

Alzheimer's Disease (AD) is a debilitating neurodegenerative disease that is diagnosed by gradual memory loss and certain cognitive impairments involving attention, reasoning, and language. Most of the research on Alzheimer's disease focuses on the correlation of its neuropathological changes in the neurofibrillary tangles caused by hyper-phosphorylated tau protein and β-amyloid plaques with respect to cognitive impairment. Its pathology, however, remains incompletely understood. Currently, research has demonstrated that environmental factors such as biometals play a crucial role in exacerbating AD progression. The present review examines the role of metals in AD progression and how metal dyshomeostasis attributes to AD pathogenesis.  It was found that certain metals possess both beneficial and harmful properties in terms of AD progression. Depending upon the concentration of the metal of interest, copper, zinc, iron, and selenium have general beneficial properties. However, when present in excess, they can lead to oxidative stress and hyperphosphorylation of tau protein, amongst other harmful effects, while calcium and magnesium were seen to have beneficial effects by regulating biometal uptake.  In this review, we have provided evidential studies that focus on the involvement of certain metals in antioxidant pathways leading to the formation of reactive species indicative of neurodegeneration.

摘要

阿尔茨海默病(AD)是一种使人衰弱的神经退行性疾病,其诊断依据是逐渐出现的记忆丧失以及涉及注意力、推理和语言的某些认知障碍。大多数关于阿尔茨海默病的研究都集中在由过度磷酸化的tau蛋白和β-淀粉样蛋白斑块引起的神经原纤维缠结中的神经病理变化与认知障碍之间的相关性。然而,其病理机制仍未完全明确。目前,研究表明生物金属等环境因素在加速AD进展中起着关键作用。本综述探讨了金属在AD进展中的作用以及金属稳态失衡如何导致AD发病机制。研究发现,某些金属在AD进展方面具有有益和有害双重特性。取决于所关注金属的浓度,铜、锌、铁和硒通常具有有益特性。然而,当它们过量存在时,会导致氧化应激和tau蛋白的过度磷酸化以及其他有害影响,而钙和镁通过调节生物金属摄取表现出有益作用。在本综述中,我们提供了一些证据研究,这些研究聚焦于某些金属参与导致指示神经退行性变的活性物质形成的抗氧化途径。

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