ArticleThe Journal of biological chemistry2015
Oligomerization and Membrane-binding Properties of Covalent Adducts Formed by the Interaction of α-Synuclein with the Toxic Dopamine Metabolite 3,4-Dihydroxyphenylacetaldehyde (DOPAL).
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 120 citations in OpenAlex.
- ALDH2 protects against dopaminergic neuronal cell ferroptosis by enhancing the enzyme activity of PRDX6 in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Peripheral catecholamine systems: an evolutionary perspective.American journal of physiology. Regulatory, integrative and comparative physiology · 2025Review
- Oxidative Stress in DNA Damage and Neurodegenerative Diseases: Unveiling The Mechanisms and Therapeutic Opportunities.Cell biochemistry and biophysics · 2025Review
- Lysine-Targeting Inhibitors of Amyloidogenic Protein Aggregation: A Promise for Neurodegenerative Proteinopathies.JACS Au · 2025Review
- CCL21-CCR7 blockade prevents neuroinflammation and degeneration in Parkinson's disease models.Journal of neuroinflammation · 2025Article
- The α-Synuclein Seeding Amplification Assay for Parkinson's Disease.International journal of molecular sciences · 2025Review
- Decoding crosstalk between neurotransmitters and α-synuclein in Parkinson's disease: pathogenesis and therapeutic implications.Therapeutic advances in neurological disorders · 2025Review
- Emerging Theories of Allostatic-Interoceptive Overload in Neurodegeneration.Current topics in behavioral neurosciences · 2025Review
- Rethinking Parkinson's disease: could dopamine reduction therapy have clinical utility?Journal of neurology · 2024Review
- Selective dopaminergic neurotoxicity modulated by inherent cell-type specific neurobiology.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
- Multiple system atrophy: an update and emerging directions of biomarkers and clinical trials.Journal of neurology · 2024Review
- Tyrosine Hydroxylase Inhibitors and Dopamine Receptor Agonists Combination Therapy for Parkinson's Disease.International journal of molecular sciences · 2024Review
- Transcriptomic profiling of early synucleinopathy in rats induced with preformed fibrils.NPJ Parkinson's disease · 2024Article
- 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
- Oxidative Stress and Neuroinflammation in Parkinson's Disease: The Role of Dopamine Oxidation Products.Antioxidants (Basel, Switzerland) · 2023Review
- Modulation of cytotoxic amyloid fibrillation and mitochondrial damage of α-synuclein by catechols mediated conformational changes.Scientific reports · 2023Article
- DOPAL initiates αSynuclein-dependent impaired proteostasis and degeneration of neuronal projections in Parkinson's disease.NPJ Parkinson's disease · 2023Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Oxidative deamination of dopamine produces the highly toxic aldehyde 3,4-dihydroxyphenylacetaldehyde (DOPAL), enhanced production of which is found in post-mortem brains of Parkinson disease patients. When injected into the substantia nigra of rat brains, DOPAL causes the loss of dopaminergic neurons accompanied by the accumulation of potentially toxic oligomers of the presynaptic protein α-synuclein (aS), potentially explaining the synergistic toxicity described for dopamine metabolism and aS aggregation. In this work, we demonstrate that DOPAL interacts with aS via formation of Schiff-base and Michael-addition adducts with Lys residues, in addition to causing oxidation of Met residues to Met-sulfoxide. DOPAL modification leads to the formation of small aS oligomers that may be cross-linked by DOPAL. Both monomeric and oligomeric DOPAL adducts potently inhibit the formation of mature amyloid fibrils by unmodified aS. The binding of aS to either lipid vesicles or detergent micelles, which results in a gain of α-helix structure in its N-terminal lipid-binding domain, protects the protein against DOPAL adduct formation and, consequently, inhibits DOPAL-induced aS oligomerization. Functionally, aS-DOPAL monomer exhibits a reduced affinity for small unilamellar vesicles with lipid composition similar to synaptic vesicles, in addition to diminished membrane-induced α-helical content in comparison with the unmodified protein. These results suggest that DOPAL could compromise the functionality of aS, even in the absence of protein oligomerization, by affecting the interaction of aS with lipid membranes and hence its role in the regulation of synaptic vesicle traffic in neurons.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.