Gerlach M, Double K L, Youdim M B H, Riederer P
Laboratory for Clinical Neurochemistry, Department of Child and Adolescence Psychiatry and Psychotherapy, University of Würzburg, Germany.
J Neural Transm Suppl. 2006(70):133-42. doi: 10.1007/978-3-211-45295-0_21.
Histopathological, biochemical and in vivo brain imaging techniques, such as magnetic resonance imaging and transcranial sonography, revealed a consistent increase of substantia nigra (SN) iron in Parkinson's disease (PD). Increased iron deposits in the SN may have genetic and non-genetic causes. There are several rare movement disorders associated with neurodegeneration, and genetic abnormalities in iron regulation resulting in iron deposition in the brain. Non-genetic causes of increased SN iron may be the result of a disturbed or open blood-brain-barrier, local changes in the normal iron-regulatory systems, intraneuronal transportation of iron from iron-rich area into the SN and release of iron from intracellular iron storage molecules. Major iron stores are ferritin and haemosiderin in glial cells as well as neuromelanin in neurons. Age- and disease dependent overload of iron storage proteins may result in iron release upon reduction. Consequently, the low molecular weight chelatable iron complexes may trigger redox reactions leading to damage of biomolecules. Additionally, upon neurodegeneration there is strong microglial activation which can be another source of high iron concentrations in the brain.
组织病理学、生物化学以及体内脑成像技术，如磁共振成像和经颅超声检查，均显示帕金森病（PD）患者黑质（SN）铁含量持续增加。SN中铁沉积增加可能有遗传和非遗传原因。有几种罕见的运动障碍与神经退行性变相关，且铁调节的基因异常会导致铁在脑内沉积。SN铁含量增加的非遗传原因可能是血脑屏障受损或开放、正常铁调节系统的局部变化、铁从富含铁的区域向SN的神经元内转运以及细胞内铁储存分子释放铁。主要的铁储存形式是胶质细胞中的铁蛋白和含铁血黄素以及神经元中的神经黑色素。铁储存蛋白随年龄和疾病的依赖性过载可能导致还原时铁的释放。因此，低分子量可螯合铁复合物可能引发氧化还原反应，导致生物分子受损。此外，神经退行性变时会有强烈的小胶质细胞激活，这可能是脑内高铁浓度的另一个来源。
