Prion protein expression level alters regional copper, iron and zinc content in the mouse brain
Prion protein expression level alters regional copper, iron and zinc content in the mouse brain
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DOI：
10.1039/c0mt00037j
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发表时间：
2011-01-01
期刊：
影响因子：
3.4
通讯作者：
George, Graham N.
中科院分区：
文献类型：
--
作者：
Pushie, M. Jake;Pickering, Ingrid J.;George, Graham N.
在过去的二十年里，Prion蛋白(PrP)在一系列致命性神经退行性疾病中的核心作用引起了人们极大的研究兴趣。此外，PrP在神经元发育中的作用，以及它在金属动态平衡中的明显作用，越来越引起人们的兴趣。宿主编码的蛋白(PrP(C))通过其N-末端结构域与多个铜原子结合，可以影响大脑中铜和铁的水平。然而，PrP(C)对调节脑内金属动态平衡和金属分布的重要性尚不完全清楚。因此，我们使用基于同步加速器的X射线荧光成像技术来绘制几种关键金属在小鼠大脑中的水平和分布，这些金属表达不同水平的PrP(C)。野生型、Prion基因敲除(PRNP(-/-))和PrP(C)过表达小鼠的脑切片显示，随着PrP(C)的表达，特定脑区的铁、铜甚至锌的水平发生了惊人的变化。我们的结果表明，PrP(C)的一个重要功能可能是调节中枢神经系统中特定金属的数量和分布。这增加了PrP(C)水平或其活性可能调节疾病进展的可能性，在这些疾病中，改变的金属稳态被认为起着致病作用，如阿尔茨海默氏症、帕金森氏病和威尔逊氏病以及血色素沉着症等疾病。
The central role of the prion protein (PrP) in a family of fatal neurodegenerate diseases has garnered considerable research interest over the past two decades. Moreover, the role of PrP in neuronal development, as well as its apparent role in metal homeostasis, is increasingly of interest. The host-encoded form of the prion protein (PrP(C)) binds multiple copper atoms via its N-terminal domain and can influence brain copper and iron levels. The importance of PrP(C) to the regulation of brain metal homeostasis and metal distribution, however, is not fully understood. We therefore employed synchrotron-based X-ray fluorescence imaging to map the level and distributions of several key metals in the brains of mice that express different levels of PrP(C). Brain sections from wild-type, prion gene knockout (Prnp(-/-)) and PrP(C) over-expressing mice revealed striking variation in the levels of iron, copper, and even zinc in specific brain regions as a function of PrP(C) expression. Our results indicate that one important function of PrP(C) may be to regulate the amount and distribution of specific metals within the central nervous system. This raises the possibility that PrP(C) levels, or its activity, might regulate the progression of diseases in which altered metal homeostasis is thought to play a pathogenic role such as Alzheimer's, Parkinson's and Wilson's diseases and disorders such as hemochromatosis.