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J Neurosci. 2015 Feb 25;35(8):3591-7. doi: 10.1523/JNEUROSCI.3439-14.2015.

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

Author information

1
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3010, Australia.
2
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3010, Australia, Elemental Bio-imaging Facility, University of Technology Sydney, Broadway, New South Wales, 2007, Australia, and Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
3
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3010, Australia, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, North Yorkshire, LS2 9JT, United Kingdom.
4
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3010, Australia, Department of Anatomical Pathology, Alfred Hospital, Prahran, Victoria 3004, Australia.
5
Neurochemistry Laboratory, Department of Psychiatry-Neuroscience, Massachusetts General Hospital (East), Charlestown, Massachusetts 02129.
6
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3010, Australia, ashley.bush@florey.edu.au.

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.

KEYWORDS:

APP; iron; nitric oxide

PMID:
25716857
DOI:
10.1523/JNEUROSCI.3439-14.2015
[Indexed for MEDLINE]
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