Intraneuronal dopamine-quinone synthesis: a review
Abstract
Dopamine-quinone is synthesized by oxidation of the catechol ring of dopamine. If this occurs within the neuronal cytosol, the quinone may react with cytosolic components, particularly with cysteine residues. In contrast, if quinone is produced within neuronal lysosomes it may provide the fundamental building block for neuromelanin. Since the population of neurons that die in Parkinson's disease are those that display obvious intralysosomal neuromelanin and since cytosolic dopamine-dependent oxyradical formation may underlie methamphetamine toxicity and other specific forms of neurodegeneration in dopaminergic neurons, it is important to elucidate the pathways leading to production of dopamine-quinone. Here we review pathways by which intracellular catechols may be oxidized to quinones, either enzymatically or via reduction of ferric iron or other metals. These metabolites can be adduced by cysteine, could underlie aberrant metabolism and ubiquitination pathways, may induce Lewy body formation, and mediate the synthesis of hydroxyl radical and oxyradical species. Finally, we suggest that by accumulating excess cytosolic catecholamine, neuromelanin synthesis may safely sequester quinones that would otherwise be produced in the neuronal cytosol.
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Catecholamines, such as dopamine, might be oxidised to highly reactive or toxic quinones via the reduction of ferric iron or enzymatically.
“Cathecolamines, such as dopamine, might be oxidised to highly reactive or toxic quinones via the reduction of ferric iron or enzymatically.65–67”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [66]
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- Authors
- Sulzer, D., & Zecca, L.
- Affiliations
- New York State Psychiatric Institute (US)
- Institute of Biomedical Technologies (IT)
- Corresponding author
- Sulzer, David
- Venue
- Neurotoxicity Research
- Published
- 1999-09
- Volume
- 1
- Issue
- 3
- Pages
- 181-195
- ISSN
- 1029-8428 (ISSN-L)
- 1476-3524
- OpenAlex
- W1966748491
- Cited by
- 284
- References
- 132
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 7 · 2023: 9 · 2022: 12 · 2021: 14 · 2020: 14 · 2019: 15 · 2018: 21 · 2017: 13 · 2016: 11 · 2015: 13 · 2014: 19 · 2013: 12 · 2012: 5
- FWCI
- 3.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neurotoxicity Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Coenzyme Q10 studies and effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- dopamine quinone, catechol oxidation, neuromelanin, Parkinson's disease, dopaminergic neurons, methamphetamine toxicity, cysteine adducts, oxyradicals, hydroxyl radicals, Lewy bodies, ubiquitination
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