Copper pathology in vulnerable brain regions in Parkinson's disease

Davies, KM; Bohic, S; Carmona, A; Ortega, R; Cottam, V; Hare, DJ; Finberg, JPM; Reyes, S; Halliday, GM; Mercer, JFB; Double, KL

Copper pathology in vulnerable brain regions in Parkinson's disease

Davies, KM Bohic, S Carmona, A Ortega, R Cottam, V Hare, DJ

Finberg, JPM Reyes, S Halliday, GM Mercer, JFB Double, KL

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Publication Type:: Journal Article
Citation:: Neurobiology of Aging, 2014, 35 (4), pp. 858 - 866
Issue Date:: 2014-04-01

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Field	Value	Language
dc.contributor.author	Davies, KM	en_US
dc.contributor.author	Bohic, S	en_US
dc.contributor.author	Carmona, A	en_US
dc.contributor.author	Ortega, R	en_US
dc.contributor.author	Cottam, V	en_US
dc.contributor.author	Hare, DJ https://orcid.org/0000-0002-5922-7643	en_US
dc.contributor.author	Finberg, JPM	en_US
dc.contributor.author	Reyes, S	en_US
dc.contributor.author	Halliday, GM	en_US
dc.contributor.author	Mercer, JFB	en_US
dc.contributor.author	Double, KL	en_US
dc.date.available	2013-09-22	en_US
dc.date.issued	2014-04-01	en_US
dc.identifier.citation	Neurobiology of Aging, 2014, 35 (4), pp. 858 - 866	en_US
dc.identifier.issn	0197-4580	en_US
dc.identifier.uri	http://hdl.handle.net/10453/32803
dc.description.abstract	Synchrotron-based x-ray fluorescence microscopy, immunofluorescence, and Western blotting were used to investigate changes in copper (Cu) and Cu-associated pathways in the vulnerable substantia nigra (SN) and locus coeruleus (LC) and in nondegenerating brain regions in cases of Parkinson's disease (PD) and appropriate healthy and disease controls. In PD and incidental Lewy body disease, levels of Cu and Cu transporter protein 1, were significantly reduced in surviving neurons in the SN and LC. Specific activity of the cuproprotein superoxide dismutase 1 was unchanged in the SN in PD but was enhanced in the parkinsonian anterior cingulate cortex, a region with α-synuclein pathology, normal Cu, and limited cell loss. These data suggest that regions affected by α-synuclein pathology may display enhanced vulnerability and cell loss if Cu-dependent protective mechanisms are compromised. Additional investigation of copper pathology in PD may identify novel targets for the development of protective therapies for this disorder. © 2014 Elsevier Inc.	en_US
dc.relation.ispartof	Neurobiology of Aging	en_US
dc.relation.isbasedon	10.1016/j.neurobiolaging.2013.09.034	en_US
dc.subject.classification	Neurology & Neurosurgery	en_US
dc.subject.mesh	Locus Coeruleus	en_US
dc.subject.mesh	Substantia Nigra	en_US
dc.subject.mesh	Gyrus Cinguli	en_US
dc.subject.mesh	Neurons	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Parkinson Disease	en_US
dc.subject.mesh	Copper	en_US
dc.subject.mesh	Superoxide Dismutase	en_US
dc.subject.mesh	Cation Transport Proteins	en_US
dc.subject.mesh	alpha-Synuclein	en_US
dc.subject.mesh	Molecular Targeted Therapy	en_US
dc.subject.mesh	Superoxide Dismutase-1	en_US
dc.subject.mesh	Copper Transporter 1	en_US
dc.title	Copper pathology in vulnerable brain regions in Parkinson's disease	en_US
dc.type	Journal Article
utslib.citation.volume	4	en_US
utslib.citation.volume	35	en_US
utslib.for	0301 Analytical Chemistry	en_US
utslib.for	1103 Clinical Sciences	en_US
utslib.for	1109 Neurosciences	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	4	en_US
pubs.publication-status	Published	en_US
pubs.volume	35	en_US

Abstract:

Synchrotron-based x-ray fluorescence microscopy, immunofluorescence, and Western blotting were used to investigate changes in copper (Cu) and Cu-associated pathways in the vulnerable substantia nigra (SN) and locus coeruleus (LC) and in nondegenerating brain regions in cases of Parkinson's disease (PD) and appropriate healthy and disease controls. In PD and incidental Lewy body disease, levels of Cu and Cu transporter protein 1, were significantly reduced in surviving neurons in the SN and LC. Specific activity of the cuproprotein superoxide dismutase 1 was unchanged in the SN in PD but was enhanced in the parkinsonian anterior cingulate cortex, a region with α-synuclein pathology, normal Cu, and limited cell loss. These data suggest that regions affected by α-synuclein pathology may display enhanced vulnerability and cell loss if Cu-dependent protective mechanisms are compromised. Additional investigation of copper pathology in PD may identify novel targets for the development of protective therapies for this disorder. © 2014 Elsevier Inc.

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

http://hdl.handle.net/10453/32803