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Characterising the spatial and temporal brain metal profile in a mouse model of tauopathy.
Metallomics ( IF 2.9 ) Pub Date : 2020-01-06 , DOI: 10.1039/c9mt00267g
Shalini S Rao 1 , Larissa Lago 1 , Raquel Gonzalez de Vega 2 , Lisa Bray 1 , Dominic J Hare 1 , David Clases 2 , Philip A Doble 2 , Paul A Adlard 1
Affiliation  

A dysregulation in the homeostasis of metals such as copper, iron and zinc is speculated to be involved in the pathogenesis of tauopathies, which includes Alzheimer's disease (AD). In particular, there is a growing body of evidence to support a role for iron in facilitating the hyperphosphorylation and aggregation of the tau protein into neurofibrillary tangles (NFTs) - a primary neuropathological hallmark of tauopathies. Therefore, the aim of this study was to characterize the spatial and temporal brain metallomic profile in a mouse model of tauopathy (rTg(tauP301L)4510), so as to provide some insight into the potential interaction between tau pathology and iron. Using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), our results revealed an age-dependent increase in brain iron levels in both WT and rTg(tauP301L)4510 mice. In addition, size exclusion chromatography-ICP-MS (SEC-ICP-MS) revealed significant age-related changes in iron bound to metalloproteins such as ferritin. The outcomes from this study may provide valuable insight into the inter-relationship between iron and tau in ageing and neurodegeneration.

中文翻译:


表征小鼠 tau 蛋白病模型中的空间和时间脑金属分布。



据推测,铜、铁和锌等金属体内平衡的失调与 tau蛋白病(包括阿尔茨海默病 (AD))的发病机制有关。特别是,越来越多的证据支持铁在促进 tau 蛋白过度磷酸化和聚集成神经原纤维缠结 (NFT) 方面的作用,这是 tau 蛋白病的主要神经病理学标志。因此,本研究的目的是表征 tau 蛋白病小鼠模型 (rTg(tauP301L)4510) 的时空脑金属组学特征,从而深入了解 tau 蛋白病理学与铁之间的潜在相互作用。使用激光烧蚀电感耦合等离子体质谱 (LA-ICP-MS),我们的结果显示 WT 和 rTg(tauP301L)4510 小鼠的脑铁水平随年龄而增加。此外,尺寸排阻色谱-ICP-MS (SEC-ICP-MS) 显示与铁蛋白等金属蛋白结合的铁与年龄相关的显着变化。这项研究的结果可能为了解铁和 tau 蛋白在衰老和神经退行性疾病中的相互关系提供有价值的见解。
更新日期:2020-02-27
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