title: Parkinson's disease iron deposition caused by nitric oxide-induced loss of β-amyloid precursor protein.
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.
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Scott
authors.identifier: http://orcid.org/0000-0002-3479-2427
authors.initials: S
authors.lastname: Ayton
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Peng
authors.identifier: http://orcid.org/0000-0001-5652-1962
authors.initials: P
authors.lastname: Lei
authors.affiliation: 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.
authors.forename: Dominic J
authors.identifier: http://orcid.org/0000-0002-5922-7643
authors.initials: DJ
authors.lastname: Hare
authors.affiliation: 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.
authors.forename: James A
authors.initials: JA
authors.lastname: Duce
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: George
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Adlard
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3010, Australia, Department of Anatomical Pathology, Alfred Hospital, Prahran, Victoria 3004, Australia.
authors.forename: Catriona
authors.initials: C
authors.lastname: McLean
authors.affiliation: Neurochemistry Laboratory, Department of Psychiatry-Neuroscience, Massachusetts General Hospital (East), Charlestown, Massachusetts 02129.
authors.forename: Jack T
authors.initials: JT
authors.lastname: Rogers
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cherny
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: David I
authors.initials: DI
authors.lastname: Finkelstein
authors.affiliation: Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3010, Australia, ashley.bush@florey.edu.au.
authors.forename: Ashley I
authors.identifier: http://orcid.org/0000-0001-8259-9069
authors.initials: AI
authors.lastname: Bush
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D059290:Dopaminergic Neurons / Q000378:metabolism; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism*; D020267:MPTP Poisoning / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology
chemical_list: D016564:Amyloid beta-Protein Precursor; D009569:Nitric Oxide; D007501:Iron
keywords: APP; iron; nitric oxide