Iron dysregulation and Parkinson's disease

Issue title: New Directions in Neuroprotection: Basic Mechanisms, Molecular Targets and Treatment Strategies

Article type: Research Article

Authors: Andersen, Julie K.

Affiliations: From the Buck Institute, 8001 Redwood Blvd, Novato, CA 94945, USA. Tel.: +1 415 209 2070; Fax: +1 415 209 2231; E-mail: [email protected]

Abstract: We have recently demonstrated that chelation of in vivo brain iron in a form which is not available to participate in oxidative events protects against a toxin-induced form of Parkinsonism in rodents, the well-established MPTP model [32]. These data strongly suggest that iron elevations observed in the Parkinsonian substantia nigra (SN), the brain region which undergoes selective neurodegeneration in the disease, are actively involved in subsequent neurodegenerative events. However the mechanism(s) by which iron levels become elevated in the Parkinsonian SN are still unclear. We hypothesize that increased oxidative stress associated with the disease may result in dysregulation of iron homeostasis in midbrain dopaminergic neurons via alterations in binding of iron regulatory proteins (IRPs). This would mechanistically explain the noted increase in cellular iron levels in the Parkinsonian SN which appear to contribute to subsequent neurodegeneration.

Keywords: Parkinson's disease, iron, oxidative stress, iron-regulatory proteins

DOI: 10.3233/JAD-2004-6S602

Journal: Journal of Alzheimer's Disease, vol. 6, no. s6, pp. S47-S52, 2004