Divalent metal transporter 1 (DMT1) contributes to neurodegeneration in animal models of Parkinson's disease

• DOI: 10.1073/pnas.0804373105
• Publication Date: 2008-11-15T01:54:26Z
• Authors: Julio Salazar; Natalia Mena; Stephane Hunot; Annick Prigent; Daniel Alvarez-Fi...; Miguel Arredondo; Charles Duyckaerts; Veronique Sazdovitch; Lin Zhao; Laura M. Garrick; Marco T. Nuñez; Michael D. Garrick; Rita Raisman-Vozari; Etienne C. Hirsch
• Keywords: DMT1; MPTP

Dopaminergic cell death in the substantia nigra (SN) is central to Parkinson's disease (PD), but neurodegenerative mechanisms have not been completely elucidated. Iron accumulation dopaminergic and glial cells SN of PD patients may contribute generation oxidative stress, protein aggregation, neuronal death. The involved iron also remain unclear. Here, we describe an increase expression isoform divalent metal transporter 1 (DMT1/Nramp2/Slc11a2) patients. Using animal model 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication mice, showed that DMT1 increases ventral mesencephalon intoxicated animals, concomitant with accumulation, loss. In addition, report a mutation impairs transport protects rodents against parkinsonism-inducing neurotoxins MPTP 6-hydroxydopamine. This study supports critical role for iron-mediated neurodegeneration PD.