Warwick Engineering in Biomedicine, School of Engineering, University of Warwick Coventry, UK ; Materials Science and Engineering, University of Florida Gainesville, FL, USA.
Materials Science and Engineering, University of Florida Gainesville, FL, USA ; The Tech Toybox, Gainesville FL, USA.
Front Pharmacol. 2014 Aug 19;5:191. doi: 10.3389/fphar.2014.00191. eCollection 2014.
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.
有证据表明，铁在许多疾病形式中失调，包括广泛的神经退行性疾病。为了深入了解铁的病理生理作用，能够详细确定铁与代谢物、蛋白质、细胞和组织的分布、铁的化学状态和局部环境以及与其他金属元素的关系，这将很有帮助。同步辐射光源主要提供 X 射线束，并可获得更长的波长，如红外线，是对这些系统中铁进行多模式非破坏性分析的出色工具。同步辐射设施产生的微焦和纳米焦 X 射线束使铁和其他过渡金属元素的测量能够具有出色的分析灵敏度和特异性。最近的发展增加了 X 射线荧光映射等方法的范围，可以进行定量而不是半定量的测量。同步辐射设施的兴趣激增、技术进步和光束线发展，使得过去十年中该领域在资源和方法方面取得了实质性的改进。在本文中，我们将考虑在蛋白质、细胞和脑组织中铁的研究方面该领域是如何发展的，并确定样品制备和分析方面的挑战。将选择一些例子来说明同步 X 射线分析对铁在表现出铁失调的模型系统中的特性描述，以及对包括阿尔茨海默病、帕金森病、弗里德里希共济失调和肌萎缩侧索硬化症在内的人类神经退行性疾病病例的研究的贡献和未来潜力。
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