Tags

Type your tag names separated by a space and hit enter

Iron transport in Parkinson's disease.
Parkinsonism Relat Disord. 2009 Dec; 15 Suppl 3:S209-11.PR

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 neurons and glial cells in the SN of PD patients may contribute to the generation of oxidative stress, protein aggregation and neuronal death. However, the mechanisms involved in iron accumulation remain unclear. In previous studies we excluded a role of transferrin and its receptor in iron accumulation while we showed that lactoferrin receptors were overexpressed in blood vessels and dopaminergic neurons in Parkinson's disease. We recently also described an increase in the expression 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 increased in the ventral mesencephalon of intoxicated animals, concomitant with iron accumulation, oxidative stress and dopaminergic cell loss. A mutation in DMT1 that impairs iron transport protected rodents against parkinsonism-inducing neurotoxins MPTP and 6-hydroxydopamine (6-OHDA). This study supports a critical role for DMT1 in iron-mediated neurodegeneration in PD.

Authors+Show Affiliations

Université Pierre & Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de Moelle Epiniére , UMR-S975, Paris, France. etienne.hirsch@upmc.fr

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20082992

Citation

Hirsch, E C.. "Iron Transport in Parkinson's Disease." Parkinsonism & Related Disorders, vol. 15 Suppl 3, 2009, pp. S209-11.
Hirsch EC. Iron transport in Parkinson's disease. Parkinsonism Relat Disord. 2009;15 Suppl 3:S209-11.
Hirsch, E. C. (2009). Iron transport in Parkinson's disease. Parkinsonism & Related Disorders, 15 Suppl 3, S209-11. https://doi.org/10.1016/S1353-8020(09)70816-8
Hirsch EC. Iron Transport in Parkinson's Disease. Parkinsonism Relat Disord. 2009;15 Suppl 3:S209-11. PubMed PMID: 20082992.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Iron transport in Parkinson's disease. A1 - Hirsch,E C, PY - 2010/1/20/entrez PY - 2010/1/30/pubmed PY - 2010/4/1/medline SP - S209 EP - 11 JF - Parkinsonism & related disorders JO - Parkinsonism Relat Disord VL - 15 Suppl 3 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 neurons and glial cells in the SN of PD patients may contribute to the generation of oxidative stress, protein aggregation and neuronal death. However, the mechanisms involved in iron accumulation remain unclear. In previous studies we excluded a role of transferrin and its receptor in iron accumulation while we showed that lactoferrin receptors were overexpressed in blood vessels and dopaminergic neurons in Parkinson's disease. We recently also described an increase in the expression 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 increased in the ventral mesencephalon of intoxicated animals, concomitant with iron accumulation, oxidative stress and dopaminergic cell loss. A mutation in DMT1 that impairs iron transport protected rodents against parkinsonism-inducing neurotoxins MPTP and 6-hydroxydopamine (6-OHDA). This study supports a critical role for DMT1 in iron-mediated neurodegeneration in PD. SN - 1873-5126 UR - https://www.unboundmedicine.com/medline/citation/20082992/Iron_transport_in_Parkinson's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1353-8020(09)70816-8 DB - PRIME DP - Unbound Medicine ER -