Ward Roberta J, Zucca Fabio A, Duyn Jeff H, Crichton Robert R, Zecca Luigi
Centre for Neuroinflammation and Neurodegeneration, Department of Medicine, Hammersmith Hospital Campus, Imperial College London, London, UK; Faculte de Science, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
Institute of Biomedical Technologies, National Research Council of Italy, Segrate, Milan, Italy.
Lancet Neurol. 2014 Oct;13(10):1045-60. doi: 10.1016/S1474-4422(14)70117-6.
In the CNS, iron in several proteins is involved in many important processes such as oxygen transportation, oxidative phosphorylation, myelin production, and the synthesis and metabolism of neurotransmitters. Abnormal iron homoeostasis can induce cellular damage through hydroxyl radical production, which can cause the oxidation and modification of lipids, proteins, carbohydrates, and DNA. During ageing, different iron complexes accumulate in brain regions associated with motor and cognitive impairment. In various neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, changes in iron homoeostasis result in altered cellular iron distribution and accumulation. MRI can often identify these changes, thus providing a potential diagnostic biomarker of neurodegenerative diseases. An important avenue to reduce iron accumulation is the use of iron chelators that are able to cross the blood-brain barrier, penetrate cells, and reduce excessive iron accumulation, thereby affording neuroprotection.
在中枢神经系统中,多种蛋白质中的铁参与许多重要过程,如氧气运输、氧化磷酸化、髓鞘生成以及神经递质的合成与代谢。铁稳态异常可通过产生羟基自由基诱导细胞损伤,这会导致脂质、蛋白质、碳水化合物和DNA的氧化与修饰。在衰老过程中,不同的铁复合物在与运动和认知障碍相关的脑区积累。在各种神经退行性疾病中,如阿尔茨海默病和帕金森病,铁稳态的变化会导致细胞内铁分布和积累的改变。磁共振成像通常能够识别这些变化,从而为神经退行性疾病提供一种潜在的诊断生物标志物。减少铁积累的一个重要途径是使用能够穿过血脑屏障、穿透细胞并减少过量铁积累的铁螯合剂,从而提供神经保护作用。