Metallobiology of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity
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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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The neurodegenerative mechanisms leading to cell death caused by the 1-methyl-4-phenylpyridinium ion are thought to involve iron and changes in iron metabolism.
“Additionally, the neurodegenerative mechanisms leading to cell death caused by the 1-methyl-4-phenylpyridinium ion are thought to involve iron and changes in iron metabolism.69”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [69]
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- Authors
- Hare, D. J., Adlard, P. A., Doble, P. A., & Finkelstein, D. I.
- Affiliations
- University of Technology Sydney (AU)
- The University of Melbourne (AU)
- Corresponding author
- Hare, Dominic J.
- Venue
- Metallomics
- Publisher
- Oxford University Press (OUP)
- Published
- 2013
- Volume
- 5
- Issue
- 2
- Pages
- 91
- ISSN
- 1756-5901 (ISSN-L)
- 1756-591X
- OpenAlex
- W2047191671
- Cited by
- 78
- References
- 188
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 9 · 2023: 3 · 2022: 4 · 2021: 10 · 2020: 4 · 2019: 8 · 2018: 1 · 2017: 7 · 2016: 6 · 2015: 10 · 2014: 6 · 2013: 2
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Metallomics (publishedVersion)
- PubMed (publishedVersion)
- OPUS - Open Publications of UTS Scholars (University of Technology Sydney) (submittedVersion)
- Funders
- Royal Society of Chemistry
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- MPTP, MPP+, Parkinson's disease, metal dyshomeostasis, iron, oxidative stress, dopaminergic neurons, substantia nigra, dopamine transporter, metal-binding proteins, neurotoxicity, MPTP model
- MeSH terms
- Humans, Models, Biological, Parkinson Disease, Substantia Nigra, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP Poisoning
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