Artículo de revista
Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson's disease
Fecha
2008Registro en:
Proceedings of the National Academy of Sciences of the United States of America, Volumen 105, Issue 47, 2018, Pages 18578-18583
00278424
10916490
10.1073/pnas.0804373105
Autor
Salazar, Julio
Mena, Natalia P.
Hunot, Stephane
Prigent, Annick
Alvarez Fischer, Daniel
Arredondo, Miguel
Duyckaerts, Charles
Sazdovitch, Veronique
Zhao, Lin
Garrick, Laura M.
Núñez González, Marco
Garrick, Michael D.
Raisman Vozari, Rita
Hirsch, Etienne C.
Institución
Resumen
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 stud