Berg D, Gerlach M, Youdim M B, Double K L, Zecca L, Riederer P, Becker G
Department of Neurology, Bayerische Julius-Maximilians-Universität Würzburg, Germany.
J Neurochem. 2001 Oct;79(2):225-36. doi: 10.1046/j.1471-4159.2001.00608.x.
A central role of iron in the pathogenesis of Parkinson's disease (PD), due to its increase in substantia nigra pars compacta dopaminergic neurons and reactive microglia and its capacity to enhance production of toxic reactive oxygen radicals, has been discussed for many years. Recent transcranial ultrasound findings and the observation of the ability of iron to induce aggregation and toxicity of alpha-synuclein have reinforced the critical role of iron in the pathogenesis of nigrostriatal injury. Presently the mechanisms involved in the disturbances of iron metabolism in PD remain obscure. In this review we summarize evidence from recent studies suggesting disturbances of iron metabolism in PD at possibly different levels including iron uptake, storage, intracellular metabolism, release and post-transcriptional control. Moreover we outline that the interaction of iron with other molecules, especially alpha-synuclein, may contribute to the process of neurodegeneration. Because many neurodegenerative diseases show increased accumulation of iron at the site of neurodegeneration, it is believed that maintenance of cellular iron homeostasis is crucial for the viability of neurons.
多年来，人们一直在探讨铁在帕金森病（PD）发病机制中的核心作用，这是由于黑质致密部多巴胺能神经元和反应性小胶质细胞中铁含量增加，以及铁增强有毒活性氧自由基生成的能力。最近的经颅超声检查结果以及铁诱导α-突触核蛋白聚集和毒性的观察结果，进一步强化了铁在黑质纹状体损伤发病机制中的关键作用。目前，PD中铁代谢紊乱所涉及的机制仍不清楚。在这篇综述中，我们总结了近期研究的证据，这些证据表明PD中铁代谢紊乱可能发生在不同水平，包括铁摄取、储存、细胞内代谢、释放和转录后调控。此外，我们概述了铁与其他分子，特别是α-突触核蛋白的相互作用，可能有助于神经退行性变过程。由于许多神经退行性疾病在神经退行性变部位显示铁积累增加，因此人们认为维持细胞铁稳态对神经元的存活至关重要。
