Journal
JOURNAL OF NEUROSCIENCE
Volume 35, Issue 8, Pages 3591-3597Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3439-14.2015
Keywords
APP; iron; nitric oxide
Categories
Funding
- Australian Research Council
- Australian National Health and Medical Research Council
- Bethlehem Griffiths Research Foundation
- University of Melbourne
- Florey Institute of Neuroscience and Mental Health
- Alfred Hospital
- Victorian Forensic Institute of Medicine
- Alzheimers Research UK [ART-SRF2011-1] Funding Source: researchfish
- Parkinson's UK [J-1203] Funding Source: researchfish
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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.
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