Although aberrant metabolism and deposition of iron has been associated with aging and neurodegeneration, the contribution of iron to neuropathology is unclear. Well-designed model systems that are suited to studying the putative pathological effect of iron are likely to be essential if such unresolved details are to be clarified. In this review, we have evaluated the utility and effectiveness of the reductionist in vitro platform to study the molecular mechanisms putatively underlying iron perturbations of neurodegenerative disease. The expression and function of iron metabolism proteins in glia and neurons and the extent to which this iron regulatory system is replicated in in vitro models has been comprehensively described, followed by an appraisal of the inherent suitability of different in vitro and ex vivo models that have been, or might be, used for iron loading. Next, we have identified and critiqued the relevant experimental parameters that have been used in in vitro iron loading experiments, including the choice of iron reagent, relevant iron loading concentrations and supplementation with serum or ascorbate, and propose optimal iron loading conditions. Finally, we have provided a synthesis of the differential iron accumulation and toxicity in glia and neurons from reported iron loading paradigms. In summary, this review has amalgamated the findings and paradigms of the published reports modelling iron loading in monocultures, discussed the limitations and discrepancies of such work to critically propose a robust, relevant and reliable model of iron loading to be used for future investigations.

尽管铁的新陈代谢和沉积与衰老和神经退行性疾病有关，但铁在神经病理学中的作用尚不清楚。如果要弄清铁的尚未解决的细节，设计良好的模型系统可能适合研究铁的假定病理效应。在这篇综述中，我们评估了还原剂体外平台的实用性和有效性，以研究潜在的铁离子引起的神经退行性疾病的分子机制。铁代谢蛋白在神经胶质和神经元中的表达和功能以及该铁调节系统在体外复制的程度对模型进行了全面描述，然后评估了已经或可能用于铁负载的不同体外和离体模型的固有适用性。接下来，我们确定并批评了已在体外使用的相关实验参数铁负载实验，包括铁试剂的选择，相关铁负载浓度以及血清或抗坏血酸的补充，并提出最佳铁负载条件。最后，我们从报告的铁负荷范例中合成了胶质细胞和神经元中不同的铁蓄积和毒性的合成。总而言之，本综述将已发表的关于单一文化中铁负载模型的报告的发现和范例进行了合并，讨论了此类工作的局限性和差异，以严谨地提出一个健壮，相关和可靠的铁负载模型，以供将来的研究使用。