Sequestration of iron by Lewy bodies in Parkinson's disease
Sequestration of iron by Lewy bodies in Parkinson's disease
复制标题
DOI：
10.1007/s004010050001
复制
发表时间：
2000-08-01
影响因子：
12.7
通讯作者：
Smith, MA
中科院分区：
文献类型：
--
作者：
Castellani, RJ;Siedlak, SL;Smith, MA
帕金森病（PD）发病机制的氧化应激假说的核心是铁通过芬顿反应产生羟基自由基的能力，以及在黑质致密部区域铁升高的一致证明。然而，过量铁是否以适合氧化还原化学的状态存在不确定性。在这里，使用我们开发的一种原位检测氧化还原活性铁的方法，我们能够在PD患者的致密黑质神经元中证明路易小体的强标记。相反，在阿尔茨海默病的路易体变异病例中，皮质路易体未染色。虽然PD中铁含量升高证实了氧化应激假说，但我们必须记住，这些是有活力的神经元，这表明路易小体可能以保护而不是退化的机制将铁隔离在PD脑中。新皮层路易体中缺乏氧化还原活性铁，这突出了皮层路易体和脑干路易体之间的根本区别。
Central to the oxidative stress hypothesis of Parkinson's disease (PD) pathogenesis is the ability of iron to generate hydroxyl radicals via the Fenton reaction, and the consistent demonstration of iron elevation in the pars compacta region of the substantia nigra. However, uncertainty exists as to whether the excess iron exists in a state suitable for redox chemistry. Here, using a method we developed that detects redox-active iron in situ, we were able to demonstrate strong labeling of Lewy bodies in substantia nigra pars compacta neurons in PD. In contrast, cortical Lewy bodies in cases of Lewy body variant of Alzheimer's disease were unstained. While the presence of elevated iron in PD substantiates the oxidative stress hypothesis, one must remember that these are viable neurons, indicating that Lewy bodies may act to sequester iron in PD brains in a protective, rather than degenerative, mechanism. The absence of redox-active iron in neocortical Lewy bodies highlights a fundamental difference between cortical and brain stem Lewy bodies.