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

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Abstract

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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Ayton, X., Lei, X., Hare, X. J., Duce, J. A., George, J. L., Adlard, P. A., … Bush, X. I. (2015). Parkinson’s disease iron deposition caused by nitric oxide- induced loss of β-amyloid precursor protein. Journal of Neuroscience, 35(8), 3591–3597. https://doi.org/10.1523/JNEUROSCI.3439-14.2015

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