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

Ayton, S; Lei, P; Hare, DJ; Duce, JA; George, JL; Adlard, PA; McLean, C; Rogers, JT; Cherny, RA; Finkelstein, DI; Bush, AI

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

Ayton, S Lei, P Hare, DJ

Duce, JA George, JL Adlard, PA McLean, C Rogers, JT Cherny, RA Finkelstein, DI Bush, AI

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Publication Type:: Journal Article
Citation:: Journal of Neuroscience, 2015, 35 (8), pp. 3591 - 3597
Issue Date:: 2015-02-25

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Field	Value	Language
dc.contributor.author	Ayton, S	en_US
dc.contributor.author	Lei, P	en_US
dc.contributor.author	Hare, DJ https://orcid.org/0000-0002-5922-7643	en_US
dc.contributor.author	Duce, JA	en_US
dc.contributor.author	George, JL	en_US
dc.contributor.author	Adlard, PA	en_US
dc.contributor.author	McLean, C	en_US
dc.contributor.author	Rogers, JT	en_US
dc.contributor.author	Cherny, RA	en_US
dc.contributor.author	Finkelstein, DI	en_US
dc.contributor.author	Bush, AI	en_US
dc.date.issued	2015-02-25	en_US
dc.identifier.citation	Journal of Neuroscience, 2015, 35 (8), pp. 3591 - 3597	en_US
dc.identifier.issn	0270-6474	en_US
dc.identifier.uri	http://hdl.handle.net/10453/35237
dc.description.abstract	© 2015 the authors. 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.	en_US
dc.relation.ispartof	Journal of Neuroscience	en_US
dc.relation.isbasedon	10.1523/JNEUROSCI.3439-14.2015	en_US
dc.subject.classification	Neurology & Neurosurgery	en_US
dc.subject.mesh	Substantia Nigra	en_US
dc.subject.mesh	Cell Line, Tumor	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred C57BL	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Parkinson Disease	en_US
dc.subject.mesh	MPTP Poisoning	en_US
dc.subject.mesh	Iron	en_US
dc.subject.mesh	Nitric Oxide	en_US
dc.subject.mesh	Amyloid beta-Protein Precursor	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Dopaminergic Neurons	en_US
dc.title	Parkinson’s disease iron deposition caused by nitric oxide- induced loss of β-amyloid precursor protein	en_US
dc.type	Journal Article
utslib.citation.volume	8	en_US
utslib.citation.volume	35	en_US
utslib.for	11 Medical and Health Sciences	en_US
utslib.for	0301 Analytical Chemistry	en_US
utslib.for	1103 Clinical Sciences	en_US
utslib.for	17 Psychology and Cognitive Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
utslib.copyright.status	closed_access
pubs.issue	8	en_US
pubs.publication-status	Published	en_US
pubs.volume	35	en_US

Abstract:

© 2015 the authors. 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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/35237