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

Scott Jonathan AytonPeng LeiDominic James HareJames A DuceJessica L GeorgePaul A AdlardCatriona McLeanJack T RogersRobert A ChernyDavid I FinkelsteinAshley I Bush
Published in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2015)
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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