Chelators in the treatment of iron accumulation in Parkinson's disease.
Chelators in the treatment of iron accumulation in Parkinson's disease.
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DOI：
10.1155/2012/983245
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发表时间：
2012
影响因子：
--
通讯作者：
Teismann P
中科院分区：
文献类型：
--
作者：
Mounsey RB;Teismann P
铁是所有细胞新陈代谢的必需元素。在包括帕金森病（PD）在内的许多神经退行性疾病患者的大脑中发现了高水平的金属。PD的发病机制在很大程度上是未知的，尽管通过实验模型的研究认为，氧化应激和脑铁稳态功能障碍，通常是一个严格调节的过程，在多巴胺能神经元的死亡中发挥重要作用。铁的积累存在于PD患者黑质中受影响的神经元和相关的小胶质细胞中。这种额外的游离铁能够产生活性氧，促进α-突触核蛋白的聚集，并加剧甚至导致神经退行性变。存在旨在逆转铁含量的这种病理性增加的各种治疗，包括合成和天然铁螯合剂。这些药物包括已建立的药物，已用于治疗与铁积累有关的其他疾病。本文将讨论铁失调如何发生，以及PD中铁增加和氧化应激之间的联系，包括这些过程导致细胞死亡的机制，然后评估目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。
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.