Buck Institute for Age Research, Novato, California 94945, USA.
J Neurochem. 2010 Jan;112(2):332-9. doi: 10.1111/j.1471-4159.2009.06470.x.
The contribution of iron dysregulation to the etiology of a variety of neuronal diseases comes as no surprise given its necessity in numerous general cellular and neuron-specific functions, its abundance, and its highly reactive nature. Homeostatic mechanisms such as the iron regulatory protein and hypoxia-inducible factor pathways are firmly evolutionarily set in place to prevent 'free' iron from participating in chemical Fenton and Haber-Weiss reactions which can result in subsequent generation of toxic hydroxyl radicals. However, given the multiple layers of complexity in cellular iron regulation, disruption of any number of genetic and environmental components can disturb the delicate balance between the various molecular players involved in maintaining an appropriate metabolic iron homeostasis. In this review, we will primarily focus on: (i) the impact of aging and gender on iron dysfunction as these are important criteria in the determination of iron-related disorders such as Parkinson's disease (PD), (ii) how iron mismanagement via disruption of cellular entry and exit pathways may contribute to these disorders, and (iii) how the availability of non-invasive measurement of brain iron may aid in PD diagnosis.
鉴于铁元素在许多一般细胞和神经元特异性功能中的必要性、丰富度以及高度反应性，铁元素调节异常对各种神经疾病病因的贡献也就不足为奇了。铁调节蛋白和缺氧诱导因子等体内平衡机制在进化上是非常稳定的，可以防止“游离”铁参与化学芬顿和哈伯-魏斯反应，从而产生有毒的羟自由基。然而，鉴于细胞中铁调节的复杂性有多个层次，任何数量的遗传和环境因素的破坏都可能打破涉及维持适当代谢铁体内平衡的各种分子参与者之间的微妙平衡。在这篇综述中，我们将主要关注：（i）年龄和性别对铁功能障碍的影响，因为这些是确定与帕金森病（PD）等铁相关疾病的重要标准，（ii）通过破坏细胞进入和退出途径的铁管理不善如何导致这些疾病，以及（iii）脑铁无创测量的可用性如何有助于 PD 的诊断。
