Parkinson's Disease Iron Deposition Caused by Nitric Oxide-Induced Loss of β-Amyloid Precursor Protein
Parkinson's Disease Iron Deposition Caused by Nitric Oxide-Induced Loss of β-Amyloid Precursor Protein
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DOI：
10.1523/jneurosci.3439-14.2015
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发表时间：
2015-02-25
影响因子：
5.3
通讯作者：
Bush, Ashley I.
中科院分区：
文献类型：
--
作者：
Ayton, Scott;Lei, Peng;Bush, Ashley I.
黑质中神经元铁和一氧化氮（NO）的升高与帕金森病（PD）的发病机制有关。我们以前报道过阿尔茨海默病相关的β -淀粉样蛋白前体蛋白（APP）促进神经元铁的输出。本研究报告了APP在人PD黑质多巴胺能神经元中的表达显著降低，APP（-/-）小鼠出现铁依赖性黑质细胞丢失。相反，过表达app的小鼠在MPTP PD模型中受到保护。NO抑制小鼠MPTP模型中的APP翻译，解释了NO升高如何导致PD中铁依赖性神经变性。
Elevation of both neuronal iron and nitric oxide (NO) in the substantia nigra are associated with Parkinson's disease (PD) pathogenesis. We reported previously that the Alzheimer-associated beta-amyloid precursor protein (APP) facilitates neuronal iron export. Here we report markedly decreased APP expression in dopaminergic neurons of human PD nigra and that APP(-/-) mice develop iron-dependent nigral cell loss. Conversely, APP-overexpressing mice are protected in the MPTP PD model. NO suppresses APP translation in mouse MPTP models, explaining how elevated NO causes iron-dependent neurodegeneration in PD.