Journal article
Parkinson’s disease iron deposition caused by nitric oxide- induced loss of β-amyloid precursor protein
X Ayton, X Lei, XJ Hare, JA Duce, JL George, PA Adlard, C McLean, JT Rogers, RA Cherny, DI Finkelstein, XI Bush
Journal of Neuroscience | Published : 2015
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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Funding Acknowledgements
This work was supported by funds from the Australian Research Council, the Australian National Health and Medical Research Council, the Bethlehem Griffiths Research Foundation, and the Operational Infrastructure Support from the Victorian State Government. The Victorian Brain Bank Network is supported by the University of Melbourne, the Florey Institute of Neuroscience and Mental Health, the Alfred Hospital, and the Victorian Forensic Institute of Medicine.