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Updated: May 15, 2026

Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
Published on: January 7, 2014
Metallobiology of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity
Dominic J Hare1, Paul A Adlard, Philip A Doble
1Elemental Bio-imaging Facility, University of Technology Sydney, New South Wales, Australia. dominic.hare@uts.edu.au
Abstract:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a potent toxin used to selectively destroy dopaminergic neurons in the substantia nigra and induce parkinsonism. MPTP is metabolised to the 1-methyl-4-phenylpyridinium ion (MPP(+)) in glia, after which it enters the neuron via the dopamine transporter and results in elevated levels of oxidative stress. The mechanism through which MPP(+) causes cell death is thought to involve redox-active metals, particularly iron (Fe). This review will examine how cellular metal metabolism is altered following MPTP insult, and how this relates to metal dyshomeostasis in idiopathic Parkinson's disease. This includes both cell damage arising from increased metal concentration, and how metal-binding proteins respond to MPTP-induced neurotoxicity. Implications for using MPTP as a model for human Parkinson's disease will be discussed in terms of cell metallobiology.
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