Clinical Neurochemistry, National Parkinson Foundation Centre of Excellence Laboratories, Clinic and Polyclinic for Psychiatry, Psychosomatic and Psychotherapy, Medical School, University of Würzburg, Würzburg, Germany.
J Neurochem. 2011 Sep;118(6):939-57. doi: 10.1111/j.1471-4159.2010.07132.x. Epub 2011 Jan 31.
Alterations of iron levels in the brain has been observed and documented in a number of neurodegenerative disorders including Parkinson's disease (PD). The elevated nigral iron levels observed in PD may reflect a dysfunction of brain iron homeostasis. Under normal physiological conditions excess iron can be sequestrated in ferritin and neuromelanin. Alternatively, the excess iron may represent a component of brain iron deposition associated with ageing. The aetiology of idiopathic PD largely remains an enigma. However, intensive investigations have provided a host of putative mechanisms that might contribute to the pathogenesis underlying the characteristic degeneration of the dopaminergic neurons in the substantia nigra (SN). The mechanisms proposed include oxidative (and nitrative) stress, inflammation, excitotoxicity, mitochondrial dysfunction, altered proteolysis and finally apoptotic induced cell death. Iron-mediated cellular destruction is mediated primarily via reactive oxygen or/and nitrogen species induced oxidative stress. Furthermore, these pathogenic mechanisms appear to be closely interlinked to the cascade of events leading to cellular death. There are conflicting reports about the stage during disease progression at which nigral iron change occurs in PD. Some have found that there are no changes in iron content SN in asymptomatic incidental Lewy body disease, suggesting it may represent a secondary event in the cascade of neuronal degeneration. In contrast, others have found an elevation of iron in SN in pre-clinical stages. These discrepancies may be attributed to the occurrence of different sub-groups of the disease. This concurs with the notion that PD represents a group of related diseases with a number of potential pathogenic pathways.
在许多神经退行性疾病中，包括帕金森病（PD），已经观察到并记录到大脑中铁水平的改变。在 PD 中观察到的升高的黑质铁水平可能反映了脑铁稳态的功能障碍。在正常生理条件下，过量的铁可以被铁蛋白和神经黑色素螯合。或者，过量的铁可能代表与衰老相关的脑铁沉积的一部分。特发性 PD 的病因在很大程度上仍然是一个谜。然而，深入的研究提供了许多可能有助于阐明黑质多巴胺能神经元特征性退化的发病机制的假设机制。提出的机制包括氧化（和硝化）应激、炎症、兴奋性毒性、线粒体功能障碍、蛋白水解改变和最终凋亡诱导的细胞死亡。铁介导的细胞破坏主要通过活性氧或/和氮物种诱导的氧化应激来介导。此外，这些致病机制似乎与导致细胞死亡的级联事件密切相关。关于 PD 中黑质铁变化发生在疾病进展的哪个阶段，存在相互矛盾的报告。一些人发现无症状偶然路易体病的 SN 中铁含量没有变化，这表明它可能代表神经元退化级联反应中的一个次要事件。相比之下，其他人在临床前阶段发现 SN 中铁的升高。这些差异可能归因于疾病的不同亚组的发生。这与 PD 代表一组相关疾病并有许多潜在的致病途径的观点一致。
