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Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson's disease.
Proc Natl Acad Sci U S A. 2008 Nov 25; 105(47):18578-83.PN

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.

Authors+Show Affiliations

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.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19011085

Citation

Salazar, Julio, et al. "Divalent Metal Transporter 1 (DMT1) Contributes to Neurodegeneration in Animal Models of Parkinson's Disease." Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 47, 2008, pp. 18578-83.
Salazar J, Mena N, Hunot S, et al. Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson's disease. Proc Natl Acad Sci U S A. 2008;105(47):18578-83.
Salazar, J., Mena, N., Hunot, S., Prigent, A., Alvarez-Fischer, D., Arredondo, M., Duyckaerts, C., Sazdovitch, V., Zhao, L., Garrick, L. M., Nuñez, M. T., Garrick, M. D., Raisman-Vozari, R., & Hirsch, E. C. (2008). Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson's disease. Proceedings of the National Academy of Sciences of the United States of America, 105(47), 18578-83. https://doi.org/10.1073/pnas.0804373105
Salazar J, et al. Divalent Metal Transporter 1 (DMT1) Contributes to Neurodegeneration in Animal Models of Parkinson's Disease. Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18578-83. PubMed PMID: 19011085.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson's disease. AU - Salazar,Julio, AU - Mena,Natalia, AU - Hunot,Stephane, AU - Prigent,Annick, AU - Alvarez-Fischer,Daniel, AU - Arredondo,Miguel, AU - Duyckaerts,Charles, AU - Sazdovitch,Veronique, AU - Zhao,Lin, AU - Garrick,Laura M, AU - Nuñez,Marco T, AU - Garrick,Michael D, AU - Raisman-Vozari,Rita, AU - Hirsch,Etienne C, Y1 - 2008/11/14/ PY - 2008/11/18/pubmed PY - 2009/1/8/medline PY - 2008/11/18/entrez SP - 18578 EP - 83 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 105 IS - 47 N2 - 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. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/19011085/Divalent_metal_transporter_1__DMT1__contributes_to_neurodegeneration_in_animal_models_of_Parkinson's_disease_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=19011085 DB - PRIME DP - Unbound Medicine ER -