title: Copper pathology in vulnerable brain regions in Parkinson's disease.
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.
authors.affiliation: Neuroscience Research Australia, Sydney, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Davies
authors.affiliation: Inserm, U836, Team 6, Rayonnement Synchrotron et Recherche Médicales, Grenoble Institut des Neurosciences, Grenoble, France; European Synchrotron Radiation Facility, BP220, Grenoble, France; Université Joseph Fourier 1, Grenoble Institut des Neurosciences, Grenoble, France. Electronic address: bohic@esrf.fr.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Bohic
authors.affiliation: University of Bordeaux, Centre d'Etudes Nucléaires de Bordeaux Gradignan, Unité Mixte de Recherche 5797, Gradignan, France; Centre National de la Recherche Scientifique, IN2P3, CENBG, UMR 5797, Gradignan, France.
authors.forename: Asunción
authors.initials: A
authors.lastname: Carmona
authors.affiliation: University of Bordeaux, Centre d'Etudes Nucléaires de Bordeaux Gradignan, Unité Mixte de Recherche 5797, Gradignan, France; Centre National de la Recherche Scientifique, IN2P3, CENBG, UMR 5797, Gradignan, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Ortega
authors.affiliation: Neuroscience Research Australia, Sydney, Australia.
authors.forename: Veronica
authors.initials: V
authors.lastname: Cottam
authors.affiliation: Elemental Bio-imaging Facility, University of Technology, Sydney, Australia; The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Hare
authors.affiliation: Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: John P M
authors.initials: JP
authors.lastname: Finberg
authors.affiliation: Neuroscience Research Australia, Sydney, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Reyes
authors.affiliation: Neuroscience Research Australia, Sydney, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
authors.affiliation: Centre for Cellular and Molecular Biology, Deakin University, Melbourne, Australia.
authors.forename: Julian F B
authors.initials: JF
authors.lastname: Mercer
authors.affiliation: Neuroscience Research Australia, Sydney, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia; Discipline of Biomedical Science, School of Medical Sciences, Sydney Medical School, The University of Sydney, Australia. Electronic address: kay.double@sydney.edu.au.
authors.forename: Kay L
authors.initials: KL
authors.lastname: Double
mesh_terms: D027682:Cation Transport Proteins / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D000079923:Copper Transporter 1; D006179:Gyrus Cinguli / Q000201:enzymology; D006801:Humans; D008125:Locus Coeruleus / Q000166:cytology / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D051844:alpha-Synuclein
chemical_list: D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; C490079:SLC31A1 protein, human; C000606290:SOD1 protein, human; D051844:alpha-Synuclein; D003300:Copper; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: Copper; Copper transporter 1 (Ctr1); Human brain; Parkinson's disease; Substantia nigra; Superoxide dismutase 1 (SOD1)