ArticleChemical research in toxicology2009
Protein reactivity of 3,4-dihydroxyphenylacetaldehyde, a toxic dopamine metabolite, is dependent on both the aldehyde and the catechol.
Article in Chemical research in toxicology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 120 citations in OpenAlex.
- α-Synuclein as a molecular link between Parkinson's disease and chronic kidney disease: insights into the kidney-brain axis.Metabolic brain disease · 2026Review
- Putamen dopamine synthesis, vesicular storage, and metabolism in Parkinson disease.medRxiv : the preprint server for health sciences · 2026Article
- Pathogenic mechanism underlying parkinsonism induced by neurotoxicants (MPTP and 6-hydroxydopamine) and α-synuclein: a unifying hypothesis.Journal of molecular cell biology · 2025Review
- ALH Inhibition as a Molecular Initiating Event in the Adverse Outcome Pathway of Benomyl Toxicity inInternational journal of molecular sciences · 2025Article
- MicroRNAs and synaptic dysfunction in Parkinson's disease.Molecular therapy. Nucleic acids · 2025Review
- Multi-omics signature of healthy versus unhealthy lifestyles reveals associations with diseases.Human genomics · 2025Article
- Not 'Inactive' After All: Cardiotoxic Mechanisms of Catecholamine Metabolism by Monoamine Oxidase.Cardiovascular toxicology · 2025Review
- Optimization of Zebrafish Larvae 6-OHDA Exposure for Neurotoxin Induced Dopaminergic Marker Reduction.Zebrafish · 2024Article
- Selective dopaminergic neurotoxicity modulated by inherent cell-type specific neurobiology.Neurotoxicology · 2024Review
- Neurotoxicology of dopamine: Victim or assailant?Neurotoxicology · 2024Review
- Sequestosome-1 (SQSTM1/p62) as a target in dopamine catabolite-mediated cellular dyshomeostasis.Cell death & disease · 2024Article
- Disruption of Dopamine Homeostasis Associated with Alteration of Proteins in Synaptic Vesicles: A Putative Central Mechanism of Parkinson's Disease Pathogenesis.Aging and disease · 2024Review
- Role of dopamine in the pathophysiology of Parkinson's disease.Translational neurodegeneration · 2023Review
- Impaired aldehyde detoxification exacerbates motor deficits in an alpha-synuclein mouse model of Parkinson's disease.Brain and behavior · 2023Article
- DOPAL initiates αSynuclein-dependent impaired proteostasis and degeneration of neuronal projections in Parkinson's disease.NPJ Parkinson's disease · 2023Article
- Alpha synuclein post translational modifications: potential targets for Parkinson's disease therapy?Frontiers in molecular neuroscience · 2023Review
- Role of Protein Damage Inflicted by Dopamine Metabolites in Parkinson's Disease: Evidence, Tools, and Outlook.Chemical research in toxicology · 2022Review
- Oxidative Transformations of 3,4-Dihydroxyphenylacetaldehyde Generate Potential Reactive Intermediates as Causative Agents for Its Neurotoxicity.International journal of molecular sciences · 2021Article
- Characterization of Catecholaldehyde Adducts with Carnosine and l-Cysteine Reveals Their Potential as Biomarkers of Catecholaminergic Stress.Chemical research in toxicology · 2021Article
- Stable expression of the human dopamine transporter in N27 cells as an in vitro model for dopamine cell trafficking and metabolism.Toxicology in vitro : an international journal published in association with BIBRA · 2021Article
23 more citing papers are in PubMed but not listed here.
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4 authors at 1 institution in 1 country.
Funding
Abstract
Dopamine (DA) has been implicated as an endogenous neurotoxin to explain selective neurodegeneration, as observed for Parkinson's disease (PD). However, previous work demonstrated that 3,4-dihydroxyphenylacetaldehyde (DOPAL) was more toxic than DA. DOPAL is generated as a part of DA catabolism via the activity of monoamine oxidase, and the mechanism of DOPAL toxicity is proposed to involve protein modification. Previous studies have demonstrated protein reactivity via the aldehyde moiety; however, DOPAL contains two reactive functional groups (catechol and aldehyde), both with the potential for protein adduction. The goal of this work was to determine whether protein modification by DOPAL occurs via a thiol-reactive quinone generated from oxidation of the catechol, which is known to occur for DA, or if the aldehyde forms adducts with amine nucleophiles. To accomplish this objective, the reactivity of DOPAL toward N-acetyl-lysine (NAL), N-acetyl-cysteine (NAC), and two model proteins was determined. In addition, several DOPAL analogues were obtained and used for comparison of reactivity. Results demonstrate that at pH 7.4 and 37 degrees C, the order of DOPAL reactivity is NAL >> NAC and the product of NAL and DOPAL is stable in the absence of reducing agent. Moreover, DOPAL will react with model proteins, but in the presence of amine-selective modifiers citraconic anhydride and 2-iminothiolane hydrochloride, the reactivity of DOPAL toward the proteins is diminished. In addition, DOPAL-mediated protein cross-linking is observed when a model protein or a protein mixture (i.e., mitochondria lysate) is treated with DOPAL at concentrations of 5-100 microM. Protein cross-linking was diminished in the presence of ascorbate, suggesting the involvement of a quinone in DOPAL-mediated protein modification. These data indicate that DOPAL is highly reactive toward protein nucleophiles with the potential for protein cross-linking.
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