Parkinson’s disease iron deposition caused by nitric oxide- induced loss of β-amyloid precursor protein

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Journal Article
Journal of Neuroscience, 2015, 35 (8), pp. 3591 - 3597
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© 2015 the authors. 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 β-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.
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