Work

Metallobiology of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity

Year: 2013

Type: review

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.

Source: Metallomics

DOI: 10.1039/c2mt20164j

Authors: Dominic J. Hare, Paul A. Adlard, Philip A. Doble, David I. Finkelstein

Institutions: University of Technology Sydney, The University of Melbourne, Florey Institute of Neuroscience and Mental Health

Language: English

Topic: Parkinson's Disease Mechanisms and Treatments

Subfield: Clinical Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: Royal Society of Chemistry