Copper pathology in vulnerable brain regions in Parkinson's disease.
Identifieur interne : 003A89 ( Main/Exploration ); précédent : 003A88; suivant : 003A90Copper pathology in vulnerable brain regions in Parkinson's disease.
Auteurs : Katherine M. Davies [Australie] ; Sylvain Bohic [France] ; Asunci N Carmona [France] ; Richard Ortega [France] ; Veronica Cottam [Australie] ; Dominic J. Hare [Australie] ; John P M. Finberg [Israël] ; Stefanie Reyes [Australie] ; Glenda M. Halliday [Australie] ; Julian F B. Mercer [Australie] ; Kay L. Double [Australie]Source :
- Neurobiology of aging [ 1558-1497 ] ; 2014.
Descripteurs français
- KwdFr :
- Cuivre (métabolisme), Gyrus du cingulum (enzymologie), Humains, Locus ceruleus (cytologie), Locus ceruleus (métabolisme), Maladie de Parkinson (génétique), Maladie de Parkinson (métabolisme), Maladie de Parkinson (traitement médicamenteux), Neurones (métabolisme), Substantia nigra (cytologie), Substantia nigra (métabolisme), Superoxide dismutase (métabolisme), Superoxide dismutase-1, Thérapie moléculaire ciblée, Transporteurs de cations (métabolisme), alpha-Synucléine.
- MESH :
- cytologie : Locus ceruleus, Substantia nigra.
- enzymologie : Gyrus du cingulum.
- génétique : Maladie de Parkinson.
- métabolisme : Cuivre, Locus ceruleus, Maladie de Parkinson, Neurones, Substantia nigra, Superoxide dismutase, Transporteurs de cations.
- traitement médicamenteux : Maladie de Parkinson.
- Humains, Superoxide dismutase-1, Thérapie moléculaire ciblée, alpha-Synucléine.
English descriptors
- KwdEn :
- Cation Transport Proteins (metabolism), Copper (metabolism), Gyrus Cinguli (enzymology), Humans, Locus Coeruleus (cytology), Locus Coeruleus (metabolism), Molecular Targeted Therapy, Neurons (metabolism), Parkinson Disease (drug therapy), Parkinson Disease (genetics), Parkinson Disease (metabolism), Substantia Nigra (cytology), Substantia Nigra (metabolism), Superoxide Dismutase (metabolism), Superoxide Dismutase-1, alpha-Synuclein.
- MESH :
- chemical , metabolism : Cation Transport Proteins, Copper, Superoxide Dismutase.
- cytology : Locus Coeruleus, Substantia Nigra.
- drug therapy : Parkinson Disease.
- enzymology : Gyrus Cinguli.
- genetics : Parkinson Disease.
- metabolism : Locus Coeruleus, Neurons, Parkinson Disease, Substantia Nigra.
- Humans, Molecular Targeted Therapy, Superoxide Dismutase-1, alpha-Synuclein.
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.
DOI: 10.1016/j.neurobiolaging.2013.09.034
PubMed: 24176624
Affiliations:
- Australie, France, Israël
- Auvergne-Rhône-Alpes, Nouvelle-Galles du Sud, Rhône-Alpes, Victoria (État)
- Grenoble, Melbourne, Sydney
- Université de Sydney
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Le document en format XML
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Davies</name><affiliation wicri:level="3"><nlm:affiliation>Neuroscience Research Australia, Sydney, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Neuroscience Research Australia, Sydney, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Bohic, Sylvain" sort="Bohic, Sylvain" uniqKey="Bohic S" first="Sylvain" last="Bohic">Sylvain Bohic</name><affiliation wicri:level="3"><nlm: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. 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Davies</name><affiliation wicri:level="3"><nlm:affiliation>Neuroscience Research Australia, Sydney, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Neuroscience Research Australia, Sydney, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Bohic, Sylvain" sort="Bohic, Sylvain" uniqKey="Bohic S" first="Sylvain" last="Bohic">Sylvain Bohic</name><affiliation wicri:level="3"><nlm: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.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>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</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Grenoble</settlement></placeName></affiliation></author><author><name sortKey="Carmona, Asunci N" sort="Carmona, Asunci N" uniqKey="Carmona A" first="Asunci N" last="Carmona">Asunci N Carmona</name><affiliation wicri:level="1"><nlm: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.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>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</wicri:regionArea><wicri:noRegion>Gradignan</wicri:noRegion><wicri:noRegion>Gradignan</wicri:noRegion></affiliation></author><author><name sortKey="Ortega, Richard" sort="Ortega, Richard" uniqKey="Ortega R" first="Richard" last="Ortega">Richard Ortega</name><affiliation wicri:level="1"><nlm: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.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>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</wicri:regionArea><wicri:noRegion>Gradignan</wicri:noRegion><wicri:noRegion>Gradignan</wicri:noRegion></affiliation></author><author><name sortKey="Cottam, Veronica" sort="Cottam, Veronica" uniqKey="Cottam V" first="Veronica" last="Cottam">Veronica Cottam</name><affiliation wicri:level="3"><nlm:affiliation>Neuroscience Research Australia, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Neuroscience Research Australia, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Hare, Dominic J" sort="Hare, Dominic J" uniqKey="Hare D" first="Dominic J" last="Hare">Dominic J. Hare</name><affiliation wicri:level="1"><nlm:affiliation>Elemental Bio-imaging Facility, University of Technology, Sydney, Australia; The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Elemental Bio-imaging Facility, University of Technology, Sydney, Australia; The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville</wicri:regionArea><wicri:noRegion>Parkville</wicri:noRegion></affiliation></author><author><name sortKey="Finberg, John P M" sort="Finberg, John P M" uniqKey="Finberg J" first="John P M" last="Finberg">John P M. Finberg</name><affiliation wicri:level="1"><nlm:affiliation>Faculty of Medicine, Technion, Haifa, Israel.</nlm:affiliation><country xml:lang="fr">Israël</country><wicri:regionArea>Faculty of Medicine, Technion, Haifa</wicri:regionArea><wicri:noRegion>Haifa</wicri:noRegion></affiliation></author><author><name sortKey="Reyes, Stefanie" sort="Reyes, Stefanie" uniqKey="Reyes S" first="Stefanie" last="Reyes">Stefanie Reyes</name><affiliation wicri:level="3"><nlm:affiliation>Neuroscience Research Australia, Sydney, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Neuroscience Research Australia, Sydney, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Halliday, Glenda M" sort="Halliday, Glenda M" uniqKey="Halliday G" first="Glenda M" last="Halliday">Glenda M. Halliday</name><affiliation wicri:level="3"><nlm:affiliation>Neuroscience Research Australia, Sydney, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Neuroscience Research Australia, Sydney, Australia; School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Mercer, Julian F B" sort="Mercer, Julian F B" uniqKey="Mercer J" first="Julian F B" last="Mercer">Julian F B. Mercer</name><affiliation wicri:level="3"><nlm:affiliation>Centre for Cellular and Molecular Biology, Deakin University, Melbourne, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Centre for Cellular and Molecular Biology, Deakin University, Melbourne</wicri:regionArea><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Double, Kay L" sort="Double, Kay L" uniqKey="Double K" first="Kay L" last="Double">Kay L. Double</name><affiliation wicri:level="4"><nlm: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.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>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</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author></analytic><series><title level="j">Neurobiology of aging</title><idno type="eISSN">1558-1497</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cation Transport Proteins (metabolism)</term><term>Copper (metabolism)</term><term>Gyrus Cinguli (enzymology)</term><term>Humans</term><term>Locus Coeruleus (cytology)</term><term>Locus Coeruleus (metabolism)</term><term>Molecular Targeted Therapy</term><term>Neurons (metabolism)</term><term>Parkinson Disease (drug therapy)</term><term>Parkinson Disease (genetics)</term><term>Parkinson Disease (metabolism)</term><term>Substantia Nigra (cytology)</term><term>Substantia Nigra (metabolism)</term><term>Superoxide Dismutase (metabolism)</term><term>Superoxide Dismutase-1</term><term>alpha-Synuclein</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Cuivre (métabolisme)</term><term>Gyrus du cingulum (enzymologie)</term><term>Humains</term><term>Locus ceruleus (cytologie)</term><term>Locus ceruleus (métabolisme)</term><term>Maladie de Parkinson (génétique)</term><term>Maladie de Parkinson (métabolisme)</term><term>Maladie de Parkinson (traitement médicamenteux)</term><term>Neurones (métabolisme)</term><term>Substantia nigra (cytologie)</term><term>Substantia nigra (métabolisme)</term><term>Superoxide dismutase (métabolisme)</term><term>Superoxide dismutase-1</term><term>Thérapie moléculaire ciblée</term><term>Transporteurs de cations (métabolisme)</term><term>alpha-Synucléine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cation Transport Proteins</term><term>Copper</term><term>Superoxide Dismutase</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Locus ceruleus</term><term>Substantia nigra</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Locus Coeruleus</term><term>Substantia Nigra</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Gyrus du cingulum</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Gyrus Cinguli</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Maladie de Parkinson</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Locus Coeruleus</term><term>Neurons</term><term>Parkinson Disease</term><term>Substantia Nigra</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cuivre</term><term>Locus ceruleus</term><term>Maladie de Parkinson</term><term>Neurones</term><term>Substantia nigra</term><term>Superoxide dismutase</term><term>Transporteurs de cations</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Maladie de Parkinson</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term><term>Molecular Targeted Therapy</term><term>Superoxide Dismutase-1</term><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Humains</term><term>Superoxide dismutase-1</term><term>Thérapie moléculaire ciblée</term><term>alpha-Synucléine</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Israël</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Nouvelle-Galles du Sud</li><li>Rhône-Alpes</li><li>Victoria (État)</li></region><settlement><li>Grenoble</li><li>Melbourne</li><li>Sydney</li></settlement><orgName><li>Université de Sydney</li></orgName></list><tree><country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="Davies, Katherine M" sort="Davies, Katherine M" uniqKey="Davies K" first="Katherine M" last="Davies">Katherine M. Davies</name></region><name sortKey="Cottam, Veronica" sort="Cottam, Veronica" uniqKey="Cottam V" first="Veronica" last="Cottam">Veronica Cottam</name><name sortKey="Double, Kay L" sort="Double, Kay L" uniqKey="Double K" first="Kay L" last="Double">Kay L. Double</name><name sortKey="Halliday, Glenda M" sort="Halliday, Glenda M" uniqKey="Halliday G" first="Glenda M" last="Halliday">Glenda M. Halliday</name><name sortKey="Hare, Dominic J" sort="Hare, Dominic J" uniqKey="Hare D" first="Dominic J" last="Hare">Dominic J. Hare</name><name sortKey="Mercer, Julian F B" sort="Mercer, Julian F B" uniqKey="Mercer J" first="Julian F B" last="Mercer">Julian F B. Mercer</name><name sortKey="Reyes, Stefanie" sort="Reyes, Stefanie" uniqKey="Reyes S" first="Stefanie" last="Reyes">Stefanie Reyes</name></country><country name="France"><region name="Auvergne-Rhône-Alpes"><name sortKey="Bohic, Sylvain" sort="Bohic, Sylvain" uniqKey="Bohic S" first="Sylvain" last="Bohic">Sylvain Bohic</name></region><name sortKey="Carmona, Asunci N" sort="Carmona, Asunci N" uniqKey="Carmona A" first="Asunci N" last="Carmona">Asunci N Carmona</name><name sortKey="Ortega, Richard" sort="Ortega, Richard" uniqKey="Ortega R" first="Richard" last="Ortega">Richard Ortega</name></country><country name="Israël"><noRegion><name sortKey="Finberg, John P M" sort="Finberg, John P M" uniqKey="Finberg J" first="John P M" last="Finberg">John P M. Finberg</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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