Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson's disease
Identifieur interne : 000932 ( Ncbi/Merge ); précédent : 000931; suivant : 000933Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson's disease
Auteurs : Julio Salazar [France, Chili] ; Natalia Mena [Chili] ; Stephane Hunot [France] ; Annick Prigent [France] ; Daniel Alvarez-Fischer [France] ; Miguel Arredondo [Chili] ; Charles Duyckaerts [France] ; Veronique Sazdovitch [France] ; Lin Zhao [États-Unis] ; Laura M. Garrick [États-Unis] ; Marco T. Nu Ez [Chili] ; Michael D. Garrick [États-Unis] ; Rita Raisman-Vozari [France] ; Etienne C. Hirsch [France]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2008.
English descriptors
- KwdEn :
- MESH :
- chemical , metabolism : Dopamine, Iron.
- chemical , physiology : Cation Transport Proteins.
- metabolism : Parkinson Disease.
- pathology : Parkinson Disease.
- physiopathology : Parkinson Disease.
- Aged, Aged, 80 and over, Animals, Disease Models, Animal, Humans, Mice, Oxidative Stress.
Abstract
Dopaminergic cell death in the substantia nigra (SN) is central to Parkinson's disease (PD), but the neurodegenerative mechanisms have not been completely elucidated. Iron accumulation in dopaminergic and glial cells in the SN of PD patients may contribute to the generation of oxidative stress, protein aggregation, and neuronal death. The mechanisms involved in iron accumulation also remain unclear. Here, we describe an increase in the expression of an isoform of the divalent metal transporter 1 (DMT1/Nramp2/Slc11a2) in the SN of PD patients. Using the PD animal model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication in mice, we showed that DMT1 expression increases in the ventral mesencephalon of intoxicated animals, concomitant with iron accumulation, oxidative stress, and dopaminergic cell loss. In addition, we report that a mutation in DMT1 that impairs iron transport protects rodents against parkinsonism-inducing neurotoxins MPTP and 6-hydroxydopamine. This study supports a critical role for DMT1 in iron-mediated neurodegeneration in PD.
Url:
DOI: 10.1073/pnas.0804373105
PubMed: 19011085
PubMed Central: 2587621
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type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Zhao, Lin" sort="Zhao, Lin" uniqKey="Zhao L" first="Lin" last="Zhao">Lin Zhao</name><affiliation wicri:level="2"><nlm:aff id="aff4">Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo, NY 14214</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo</wicri:cityArea></affiliation></author><author><name sortKey="Garrick, Laura M" sort="Garrick, Laura M" uniqKey="Garrick L" first="Laura M." last="Garrick">Laura M. Garrick</name><affiliation wicri:level="2"><nlm:aff id="aff4">Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo, NY 14214</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo</wicri:cityArea></affiliation></author><author><name sortKey="Nu Ez, Marco T" sort="Nu Ez, Marco T" uniqKey="Nu Ez M" first="Marco T." last="Nu Ez">Marco T. Nu Ez</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff3">Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago, Chile</nlm:aff><country xml:lang="fr">Chili</country><wicri:regionArea>Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago</wicri:regionArea><wicri:noRegion>Santiago</wicri:noRegion></affiliation></author><author><name sortKey="Garrick, Michael D" sort="Garrick, Michael D" uniqKey="Garrick M" first="Michael D." last="Garrick">Michael D. Garrick</name><affiliation wicri:level="2"><nlm:aff id="aff4">Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo, NY 14214</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo</wicri:cityArea></affiliation></author><author><name sortKey="Raisman Vozari, Rita" sort="Raisman Vozari, Rita" uniqKey="Raisman Vozari R" first="Rita" last="Raisman-Vozari">Rita Raisman-Vozari</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C." last="Hirsch">Etienne C. 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S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff3">Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago, Chile</nlm:aff><country xml:lang="fr">Chili</country><wicri:regionArea>Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago</wicri:regionArea><wicri:noRegion>Santiago</wicri:noRegion></affiliation></author><author><name sortKey="Mena, Natalia" sort="Mena, Natalia" uniqKey="Mena N" first="Natalia" last="Mena">Natalia Mena</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff3">Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago, Chile</nlm:aff><country xml:lang="fr">Chili</country><wicri:regionArea>Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago</wicri:regionArea><wicri:noRegion>Santiago</wicri:noRegion></affiliation></author><author><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stephane" last="Hunot">Stephane Hunot</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Prigent, Annick" sort="Prigent, Annick" uniqKey="Prigent A" first="Annick" last="Prigent">Annick Prigent</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Alvarez Fischer, Daniel" sort="Alvarez Fischer, Daniel" uniqKey="Alvarez Fischer D" first="Daniel" last="Alvarez-Fischer">Daniel Alvarez-Fischer</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Arredondo, Miguel" sort="Arredondo, Miguel" uniqKey="Arredondo M" first="Miguel" last="Arredondo">Miguel Arredondo</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff3">Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago, Chile</nlm:aff><country xml:lang="fr">Chili</country><wicri:regionArea>Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago</wicri:regionArea><wicri:noRegion>Santiago</wicri:noRegion></affiliation></author><author><name sortKey="Duyckaerts, Charles" sort="Duyckaerts, Charles" uniqKey="Duyckaerts C" first="Charles" last="Duyckaerts">Charles Duyckaerts</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Sazdovitch, Veronique" sort="Sazdovitch, Veronique" uniqKey="Sazdovitch V" first="Veronique" last="Sazdovitch">Veronique Sazdovitch</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Zhao, Lin" sort="Zhao, Lin" uniqKey="Zhao L" first="Lin" last="Zhao">Lin Zhao</name><affiliation wicri:level="2"><nlm:aff id="aff4">Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo, NY 14214</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo</wicri:cityArea></affiliation></author><author><name sortKey="Garrick, Laura M" sort="Garrick, Laura M" uniqKey="Garrick L" first="Laura M." last="Garrick">Laura M. Garrick</name><affiliation wicri:level="2"><nlm:aff id="aff4">Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo, NY 14214</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo</wicri:cityArea></affiliation></author><author><name sortKey="Nu Ez, Marco T" sort="Nu Ez, Marco T" uniqKey="Nu Ez M" first="Marco T." last="Nu Ez">Marco T. Nu Ez</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff3">Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago, Chile</nlm:aff><country xml:lang="fr">Chili</country><wicri:regionArea>Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago</wicri:regionArea><wicri:noRegion>Santiago</wicri:noRegion></affiliation></author><author><name sortKey="Garrick, Michael D" sort="Garrick, Michael D" uniqKey="Garrick M" first="Michael D." last="Garrick">Michael D. Garrick</name><affiliation wicri:level="2"><nlm:aff id="aff4">Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo, NY 14214</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo</wicri:cityArea></affiliation></author><author><name sortKey="Raisman Vozari, Rita" sort="Raisman Vozari, Rita" uniqKey="Raisman Vozari R" first="Rita" last="Raisman-Vozari">Rita Raisman-Vozari</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C." last="Hirsch">Etienne C. Hirsch</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Animals</term><term>Cation Transport Proteins (physiology)</term><term>Disease Models, Animal</term><term>Dopamine (metabolism)</term><term>Humans</term><term>Iron (metabolism)</term><term>Mice</term><term>Oxidative Stress</term><term>Parkinson Disease (metabolism)</term><term>Parkinson Disease (pathology)</term><term>Parkinson Disease (physiopathology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term><term>Iron</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Cation Transport Proteins</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Animals</term><term>Disease Models, Animal</term><term>Humans</term><term>Mice</term><term>Oxidative Stress</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Dopaminergic cell death in the substantia nigra (SN) is central to Parkinson's disease (PD), but the neurodegenerative mechanisms have not been completely elucidated. Iron accumulation in dopaminergic and glial cells in the SN of PD patients may contribute to the generation of oxidative stress, protein aggregation, and neuronal death. The mechanisms involved in iron accumulation also remain unclear. Here, we describe an increase in the expression of an isoform of the divalent metal transporter 1 (DMT1/Nramp2/Slc11a2) in the SN of PD patients. Using the PD animal model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication in mice, we showed that DMT1 expression increases in the ventral mesencephalon of intoxicated animals, concomitant with iron accumulation, oxidative stress, and dopaminergic cell loss. In addition, we report that a mutation in DMT1 that impairs iron transport protects rodents against parkinsonism-inducing neurotoxins MPTP and 6-hydroxydopamine. This study supports a critical role for DMT1 in iron-mediated neurodegeneration in PD.</p></div></front></TEI><double pmid="19011085"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson's disease</title><author><name sortKey="Salazar, Julio" sort="Salazar, Julio" uniqKey="Salazar J" first="Julio" last="Salazar">Julio Salazar</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff3">Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago, Chile</nlm:aff><country xml:lang="fr">Chili</country><wicri:regionArea>Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago</wicri:regionArea><wicri:noRegion>Santiago</wicri:noRegion></affiliation></author><author><name sortKey="Mena, Natalia" sort="Mena, Natalia" uniqKey="Mena N" first="Natalia" last="Mena">Natalia Mena</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff3">Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago, Chile</nlm:aff><country xml:lang="fr">Chili</country><wicri:regionArea>Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago</wicri:regionArea><wicri:noRegion>Santiago</wicri:noRegion></affiliation></author><author><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stephane" last="Hunot">Stephane Hunot</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Prigent, Annick" sort="Prigent, Annick" uniqKey="Prigent A" first="Annick" last="Prigent">Annick Prigent</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Alvarez Fischer, Daniel" sort="Alvarez Fischer, Daniel" uniqKey="Alvarez Fischer D" first="Daniel" last="Alvarez-Fischer">Daniel Alvarez-Fischer</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Arredondo, Miguel" sort="Arredondo, Miguel" uniqKey="Arredondo M" first="Miguel" last="Arredondo">Miguel Arredondo</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff3">Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago, Chile</nlm:aff><country xml:lang="fr">Chili</country><wicri:regionArea>Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago</wicri:regionArea><wicri:noRegion>Santiago</wicri:noRegion></affiliation></author><author><name sortKey="Duyckaerts, Charles" sort="Duyckaerts, Charles" uniqKey="Duyckaerts C" first="Charles" last="Duyckaerts">Charles Duyckaerts</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Sazdovitch, Veronique" sort="Sazdovitch, Veronique" uniqKey="Sazdovitch V" first="Veronique" last="Sazdovitch">Veronique Sazdovitch</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Zhao, Lin" sort="Zhao, Lin" uniqKey="Zhao L" first="Lin" last="Zhao">Lin Zhao</name><affiliation wicri:level="2"><nlm:aff id="aff4">Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo, NY 14214</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo</wicri:cityArea></affiliation></author><author><name sortKey="Garrick, Laura M" sort="Garrick, Laura M" uniqKey="Garrick L" first="Laura M." last="Garrick">Laura M. Garrick</name><affiliation wicri:level="2"><nlm:aff id="aff4">Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo, NY 14214</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo</wicri:cityArea></affiliation></author><author><name sortKey="Nu Ez, Marco T" sort="Nu Ez, Marco T" uniqKey="Nu Ez M" first="Marco T." last="Nu Ez">Marco T. Nu Ez</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff3">Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago, Chile</nlm:aff><country xml:lang="fr">Chili</country><wicri:regionArea>Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago</wicri:regionArea><wicri:noRegion>Santiago</wicri:noRegion></affiliation></author><author><name sortKey="Garrick, Michael D" sort="Garrick, Michael D" uniqKey="Garrick M" first="Michael D." last="Garrick">Michael D. Garrick</name><affiliation wicri:level="2"><nlm:aff id="aff4">Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo, NY 14214</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo</wicri:cityArea></affiliation></author><author><name sortKey="Raisman Vozari, Rita" sort="Raisman Vozari, Rita" uniqKey="Raisman Vozari R" first="Rita" last="Raisman-Vozari">Rita Raisman-Vozari</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C." last="Hirsch">Etienne C. Hirsch</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19011085</idno><idno type="pmc">2587621</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587621</idno><idno type="RBID">PMC:2587621</idno><idno type="doi">10.1073/pnas.0804373105</idno><date when="2008">2008</date><idno type="wicri:Area/Pmc/Corpus">000532</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000532</idno><idno type="wicri:Area/Pmc/Curation">000529</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000529</idno><idno type="wicri:Area/Pmc/Checkpoint">000859</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000859</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson's disease</title><author><name sortKey="Salazar, Julio" sort="Salazar, Julio" uniqKey="Salazar J" first="Julio" last="Salazar">Julio Salazar</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff3">Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago, Chile</nlm:aff><country xml:lang="fr">Chili</country><wicri:regionArea>Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago</wicri:regionArea><wicri:noRegion>Santiago</wicri:noRegion></affiliation></author><author><name sortKey="Mena, Natalia" sort="Mena, Natalia" uniqKey="Mena N" first="Natalia" last="Mena">Natalia Mena</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff3">Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago, Chile</nlm:aff><country xml:lang="fr">Chili</country><wicri:regionArea>Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago</wicri:regionArea><wicri:noRegion>Santiago</wicri:noRegion></affiliation></author><author><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stephane" last="Hunot">Stephane Hunot</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Prigent, Annick" sort="Prigent, Annick" uniqKey="Prigent A" first="Annick" last="Prigent">Annick Prigent</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Alvarez Fischer, Daniel" sort="Alvarez Fischer, Daniel" uniqKey="Alvarez Fischer D" first="Daniel" last="Alvarez-Fischer">Daniel Alvarez-Fischer</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Arredondo, Miguel" sort="Arredondo, Miguel" uniqKey="Arredondo M" first="Miguel" last="Arredondo">Miguel Arredondo</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff3">Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago, Chile</nlm:aff><country xml:lang="fr">Chili</country><wicri:regionArea>Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago</wicri:regionArea><wicri:noRegion>Santiago</wicri:noRegion></affiliation></author><author><name sortKey="Duyckaerts, Charles" sort="Duyckaerts, Charles" uniqKey="Duyckaerts C" first="Charles" last="Duyckaerts">Charles Duyckaerts</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Sazdovitch, Veronique" sort="Sazdovitch, Veronique" uniqKey="Sazdovitch V" first="Veronique" last="Sazdovitch">Veronique Sazdovitch</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Zhao, Lin" sort="Zhao, Lin" uniqKey="Zhao L" first="Lin" last="Zhao">Lin Zhao</name><affiliation wicri:level="2"><nlm:aff id="aff4">Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo, NY 14214</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo</wicri:cityArea></affiliation></author><author><name sortKey="Garrick, Laura M" sort="Garrick, Laura M" uniqKey="Garrick L" first="Laura M." last="Garrick">Laura M. Garrick</name><affiliation wicri:level="2"><nlm:aff id="aff4">Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo, NY 14214</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo</wicri:cityArea></affiliation></author><author><name sortKey="Nu Ez, Marco T" sort="Nu Ez, Marco T" uniqKey="Nu Ez M" first="Marco T." last="Nu Ez">Marco T. Nu Ez</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff3">Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago, Chile</nlm:aff><country xml:lang="fr">Chili</country><wicri:regionArea>Millennium Institute for Cell Dynamics and Biotechnology and Department of Biology, Faculty of Sciences, Universidad de Chile, Las Encinas 3370, Santiago</wicri:regionArea><wicri:noRegion>Santiago</wicri:noRegion></affiliation></author><author><name sortKey="Garrick, Michael D" sort="Garrick, Michael D" uniqKey="Garrick M" first="Michael D." last="Garrick">Michael D. Garrick</name><affiliation wicri:level="2"><nlm:aff id="aff4">Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo, NY 14214</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Biochemistry, University at Buffalo, State University of New York, 140 Farber Hall, 3435 Main Street, Buffalo</wicri:cityArea></affiliation></author><author><name sortKey="Raisman Vozari, Rita" sort="Raisman Vozari, Rita" uniqKey="Raisman Vozari R" first="Rita" last="Raisman-Vozari">Rita Raisman-Vozari</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C." last="Hirsch">Etienne C. Hirsch</name><affiliation wicri:level="3"><nlm:aff id="aff1">Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2">Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité Mixte de Recherche S679, Université Pierre et Marie Curie, Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Dopaminergic cell death in the substantia nigra (SN) is central to Parkinson's disease (PD), but the neurodegenerative mechanisms have not been completely elucidated. Iron accumulation in dopaminergic and glial cells in the SN of PD patients may contribute to the generation of oxidative stress, protein aggregation, and neuronal death. The mechanisms involved in iron accumulation also remain unclear. Here, we describe an increase in the expression of an isoform of the divalent metal transporter 1 (DMT1/Nramp2/Slc11a2) in the SN of PD patients. Using the PD animal model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication in mice, we showed that DMT1 expression increases in the ventral mesencephalon of intoxicated animals, concomitant with iron accumulation, oxidative stress, and dopaminergic cell loss. In addition, we report that a mutation in DMT1 that impairs iron transport protects rodents against parkinsonism-inducing neurotoxins MPTP and 6-hydroxydopamine. This study supports a critical role for DMT1 in iron-mediated neurodegeneration in PD.</p></div></front></TEI></pmc><pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson's disease.</title><author><name sortKey="Salazar, Julio" sort="Salazar, Julio" uniqKey="Salazar J" first="Julio" last="Salazar">Julio Salazar</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Mena, Natalia" sort="Mena, Natalia" uniqKey="Mena N" first="Natalia" last="Mena">Natalia Mena</name></author><author><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stephane" last="Hunot">Stephane Hunot</name></author><author><name sortKey="Prigent, Annick" sort="Prigent, Annick" uniqKey="Prigent A" first="Annick" last="Prigent">Annick Prigent</name></author><author><name sortKey="Alvarez Fischer, Daniel" sort="Alvarez Fischer, Daniel" uniqKey="Alvarez Fischer D" first="Daniel" last="Alvarez-Fischer">Daniel Alvarez-Fischer</name></author><author><name sortKey="Arredondo, Miguel" sort="Arredondo, Miguel" uniqKey="Arredondo M" first="Miguel" last="Arredondo">Miguel Arredondo</name></author><author><name sortKey="Duyckaerts, Charles" sort="Duyckaerts, Charles" uniqKey="Duyckaerts C" first="Charles" last="Duyckaerts">Charles Duyckaerts</name></author><author><name sortKey="Sazdovitch, Veronique" sort="Sazdovitch, Veronique" uniqKey="Sazdovitch V" first="Veronique" last="Sazdovitch">Veronique Sazdovitch</name></author><author><name sortKey="Zhao, Lin" sort="Zhao, Lin" uniqKey="Zhao L" first="Lin" last="Zhao">Lin Zhao</name></author><author><name sortKey="Garrick, Laura M" sort="Garrick, Laura M" uniqKey="Garrick L" first="Laura M" last="Garrick">Laura M. Garrick</name></author><author><name sortKey="Nu Ez, Marco T" sort="Nu Ez, Marco T" uniqKey="Nu Ez M" first="Marco T" last="Nu Ez">Marco T. Nu Ez</name></author><author><name sortKey="Garrick, Michael D" sort="Garrick, Michael D" uniqKey="Garrick M" first="Michael D" last="Garrick">Michael D. Garrick</name></author><author><name sortKey="Raisman Vozari, Rita" sort="Raisman Vozari, Rita" uniqKey="Raisman Vozari R" first="Rita" last="Raisman-Vozari">Rita Raisman-Vozari</name></author><author><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C" last="Hirsch">Etienne C. Hirsch</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2008">2008</date><idno type="RBID">pubmed:19011085</idno><idno type="pmid">19011085</idno><idno type="doi">10.1073/pnas.0804373105</idno><idno type="wicri:Area/PubMed/Corpus">000C47</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000C47</idno><idno type="wicri:Area/PubMed/Curation">000C07</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000C07</idno><idno type="wicri:Area/PubMed/Checkpoint">000C07</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000C07</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson's disease.</title><author><name sortKey="Salazar, Julio" sort="Salazar, Julio" uniqKey="Salazar J" first="Julio" last="Salazar">Julio Salazar</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, Neurologie et Thérapeutique Expérimentale, Unité Mixte de Recherche S679, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Mena, Natalia" sort="Mena, Natalia" uniqKey="Mena N" first="Natalia" last="Mena">Natalia Mena</name></author><author><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stephane" last="Hunot">Stephane Hunot</name></author><author><name sortKey="Prigent, Annick" sort="Prigent, Annick" uniqKey="Prigent A" first="Annick" last="Prigent">Annick Prigent</name></author><author><name sortKey="Alvarez Fischer, Daniel" sort="Alvarez Fischer, Daniel" uniqKey="Alvarez Fischer D" first="Daniel" last="Alvarez-Fischer">Daniel Alvarez-Fischer</name></author><author><name sortKey="Arredondo, Miguel" sort="Arredondo, Miguel" uniqKey="Arredondo M" first="Miguel" last="Arredondo">Miguel Arredondo</name></author><author><name sortKey="Duyckaerts, Charles" sort="Duyckaerts, Charles" uniqKey="Duyckaerts C" first="Charles" last="Duyckaerts">Charles Duyckaerts</name></author><author><name sortKey="Sazdovitch, Veronique" sort="Sazdovitch, Veronique" uniqKey="Sazdovitch V" first="Veronique" last="Sazdovitch">Veronique Sazdovitch</name></author><author><name sortKey="Zhao, Lin" sort="Zhao, Lin" uniqKey="Zhao L" first="Lin" last="Zhao">Lin Zhao</name></author><author><name sortKey="Garrick, Laura M" sort="Garrick, Laura M" uniqKey="Garrick L" first="Laura M" last="Garrick">Laura M. Garrick</name></author><author><name sortKey="Nu Ez, Marco T" sort="Nu Ez, Marco T" uniqKey="Nu Ez M" first="Marco T" last="Nu Ez">Marco T. Nu Ez</name></author><author><name sortKey="Garrick, Michael D" sort="Garrick, Michael D" uniqKey="Garrick M" first="Michael D" last="Garrick">Michael D. Garrick</name></author><author><name sortKey="Raisman Vozari, Rita" sort="Raisman Vozari, Rita" uniqKey="Raisman Vozari R" first="Rita" last="Raisman-Vozari">Rita Raisman-Vozari</name></author><author><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C" last="Hirsch">Etienne C. Hirsch</name></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="eISSN">1091-6490</idno><imprint><date when="2008" type="published">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Animals</term><term>Cation Transport Proteins (physiology)</term><term>Disease Models, Animal</term><term>Dopamine (metabolism)</term><term>Humans</term><term>Iron (metabolism)</term><term>Mice</term><term>Oxidative Stress</term><term>Parkinson Disease (metabolism)</term><term>Parkinson Disease (pathology)</term><term>Parkinson Disease (physiopathology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term><term>Iron</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Cation Transport Proteins</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Animals</term><term>Disease Models, Animal</term><term>Humans</term><term>Mice</term><term>Oxidative Stress</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Dopaminergic cell death in the substantia nigra (SN) is central to Parkinson's disease (PD), but the neurodegenerative mechanisms have not been completely elucidated. Iron accumulation in dopaminergic and glial cells in the SN of PD patients may contribute to the generation of oxidative stress, protein aggregation, and neuronal death. The mechanisms involved in iron accumulation also remain unclear. Here, we describe an increase in the expression of an isoform of the divalent metal transporter 1 (DMT1/Nramp2/Slc11a2) in the SN of PD patients. Using the PD animal model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication in mice, we showed that DMT1 expression increases in the ventral mesencephalon of intoxicated animals, concomitant with iron accumulation, oxidative stress, and dopaminergic cell loss. In addition, we report that a mutation in DMT1 that impairs iron transport protects rodents against parkinsonism-inducing neurotoxins MPTP and 6-hydroxydopamine. This study supports a critical role for DMT1 in iron-mediated neurodegeneration in PD.</div></front></TEI></pubmed></double></record>Pour manipuler ce document sous Unix (Dilib)
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