The role of iron in neurodegenerative disorders: insights and opportunities with synchrotron light.
The role of iron in neurodegenerative disorders: insights and opportunities with synchrotron light.
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DOI：
10.3389/fphar.2014.00191
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发表时间：
2014
影响因子：
5.6
通讯作者：
Davidson MR
中科院分区：
文献类型：
--
作者：
Collingwood JF;Davidson MR
有证据表明，在许多形式的疾病，包括广泛的神经退行性疾病铁失调。为了进一步了解铁的病理生理作用，详细确定铁的分布与代谢物、蛋白质、细胞和组织、铁的化学状态和局部环境以及与其他金属元素的关系是有帮助的。同步加速器光源，主要提供x射线光束，伴随着更长的波长，如红外线，是这些系统中铁的多模态非破坏性分析的杰出工具。同步加速器设备产生的微和纳米聚焦x射线束使铁和其他过渡金属元素的测量能够以出色的分析灵敏度和特异性进行。最近的发展扩大了定量而不是半定量地使用x射线荧光作图等方法的范围。在过去的十年里，随着同步加速器设施的技术进步和光束线的发展，人们的兴趣日益浓厚，这导致了该领域资源和方法的实质性改进。在本文中，我们将考虑该领域在蛋白质、细胞和脑组织中铁的研究方面是如何发展的，并确定样品制备和分析中的挑战。选定的例子将用于说明同步加速器x射线分析的贡献和未来潜力，以表征铁失调模型系统中的铁，以及人类神经退行性疾病，包括阿尔茨海默病，帕金森病，弗里德赖希共济失调和肌萎缩性侧索硬化症。
There is evidence for iron dysregulation in many forms of disease, including a broad spectrum of neurodegenerative disorders. In order to advance our understanding of the pathophysiological role of iron, it is helpful to be able to determine in detail the distribution of iron as it relates to metabolites, proteins, cells, and tissues, the chemical state and local environment of iron, and its relationship with other metal elements. Synchrotron light sources, providing primarily X-ray beams accompanied by access to longer wavelengths such as infra-red, are an outstanding tool for multi-modal non-destructive analysis of iron in these systems. The micro- and nano-focused X-ray beams that are generated at synchrotron facilities enable measurement of iron and other transition metal elements to be performed with outstanding analytic sensitivity and specificity. Recent developments have increased the scope for methods such as X-ray fluorescence mapping to be used quantitatively rather than semi-quantitatively. Burgeoning interest, coupled with technical advances and beamline development at synchrotron facilities, has led to substantial improvements in resources and methodologies in the field over the past decade. In this paper we will consider how the field has evolved with regard to the study of iron in proteins, cells, and brain tissue, and identify challenges in sample preparation and analysis. Selected examples will be used to illustrate the contribution, and future potential, of synchrotron X-ray analysis for the characterization of iron in model systems exhibiting iron dysregulation, and for human cases of neurodegenerative disorders including Alzheimer’s disease, Parkinson’s disease, Friedreich’s ataxia, and amyotrophic lateral sclerosis.
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