Mounsey Ross B, Teismann Peter
School of Medical Sciences, College of Life Sciences and Medicine Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Int J Cell Biol. 2012;2012:983245. doi: 10.1155/2012/983245. Epub 2012 Jun 13.
Iron is an essential element in the metabolism of all cells. Elevated levels of the metal have been found in the brains of patients of numerous neurodegenerative disorders, including Parkinson's disease (PD). The pathogenesis of PD is largely unknown, although it is thought through studies with experimental models that oxidative stress and dysfunction of brain iron homeostasis, usually a tightly regulated process, play significant roles in the death of dopaminergic neurons. Accumulation of iron is present at affected neurons and associated microglia in the substantia nigra of PD patients. This additional free-iron has the capacity to generate reactive oxygen species, promote the aggregation of α-synuclein protein, and exacerbate or even cause neurodegeneration. There are various treatments aimed at reversing this pathologic increase in iron content, comprising both synthetic and natural iron chelators. These include established drugs, which have been used to treat other disorders related to iron accumulation. This paper will discuss how iron dysregulation occurs and the link between increased iron and oxidative stress in PD, including the mechanism by which these processes lead to cell death, before assessing the current pharmacotherapies aimed at restoring normal iron redox and new chelation strategies undergoing research.
铁是所有细胞新陈代谢中的必需元素。在包括帕金森病（PD）在内的众多神经退行性疾病患者的大脑中，已发现该金属水平升高。尽管通过实验模型研究认为，氧化应激和脑铁稳态功能障碍（通常是一个严格调控的过程）在多巴胺能神经元死亡中起重要作用，但PD的发病机制在很大程度上仍不清楚。铁的积累存在于PD患者黑质中受影响的神经元和相关小胶质细胞中。这种额外的游离铁有能力产生活性氧，促进α-突触核蛋白的聚集，并加剧甚至导致神经退行性变。有多种旨在逆转这种铁含量病理性增加的治疗方法，包括合成和天然铁螯合剂。这些包括已用于治疗其他与铁积累相关疾病的既定药物。在评估当前旨在恢复正常铁氧化还原的药物治疗和正在研究的新螯合策略之前，本文将讨论铁调节异常是如何发生的以及PD中铁增加与氧化应激之间的联系，包括这些过程导致细胞死亡的机制。
