ArticleNPJ Parkinson's disease2023
DOPAL initiates αSynuclein-dependent impaired proteostasis and degeneration of neuronal projections in Parkinson's disease.
Article in NPJ Parkinson's disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
- Neurotransmitter Dysregulation in Parkinson's Disease: Pathophysiological Insights and Therapeutic Perspectives.ACS chemical neuroscience · 2026Review
- Discovery of newborn Wilson disease biomarkers via integrated next-generation sequencing and untargeted metabolomics.Orphanet journal of rare diseases · 2025Article
- 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
- CCL21-CCR7 blockade prevents neuroinflammation and degeneration in Parkinson's disease models.Journal of neuroinflammation · 2025Article
- Reversing Signs of Parkinsonism in a Cell Model Using Mitochondria-Targeted Organoiridium Catalysis.Journal of medicinal chemistry · 2025Article
- Mitochondrial Dysfunction in Parkinson's Disease: A Contribution to Cognitive Impairment?International journal of molecular sciences · 2024Review
- Natural Compounds That Activate the KEAP1/Nrf2 Signaling Pathway as Potential New Drugs in the Treatment of Idiopathic Parkinson's Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Calbindin and Girk2/Aldh1a1 define resilient vs vulnerable dopaminergic neurons in a primate Parkinson's disease model.NPJ Parkinson's disease · 2024Article
- 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
- Targets to Search for New Pharmacological Treatment in Idiopathic Parkinson's Disease According to the Single-Neuron Degeneration Model.Biomolecules · 2024Review
- Current trends in basic research on Parkinson's disease: from mitochondria, lysosome to α-synuclein.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- 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
- Tyrosine Hydroxylase Inhibitors and Dopamine Receptor Agonists Combination Therapy for Parkinson's Disease.International journal of molecular sciences · 2024Review
- A SPLICS reporter reveals [Formula: see text]-synuclein regulation of lysosome-mitochondria contacts which affects TFEB nuclear translocation.Nature communications · 2024Article
- Cardiac noradrenergic deficiency revealed by 18F-dopamine positron emission tomography identifies preclinical central Lewy body diseases.The Journal of clinical investigation · 2024Article
- Neuroprotective Effect of Antiapoptotic URG7 Protein on Human Neuroblastoma Cell Line SH-SY5Y.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
Abstract
Dopamine dyshomeostasis has been acknowledged among the determinants of nigrostriatal neuron degeneration in Parkinson's disease (PD). Several studies in experimental models and postmortem PD patients underlined increasing levels of the dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is highly reactive towards proteins. DOPAL has been shown to covalently modify the presynaptic protein αSynuclein (αSyn), whose misfolding and aggregation represent a major trait of PD pathology, triggering αSyn oligomerization in dopaminergic neurons. Here, we demonstrated that DOPAL elicits αSyn accumulation and hampers αSyn clearance in primary neurons. DOPAL-induced αSyn buildup lessens neuronal resilience, compromises synaptic integrity, and overwhelms protein quality control pathways in neurites. The progressive decline of neuronal homeostasis further leads to dopaminergic neuron loss and motor impairment, as showed in in vivo models. Finally, we developed a specific antibody which detected increased DOPAL-modified αSyn in human striatal tissues from idiopathic PD patients, corroborating the translational relevance of αSyn-DOPAL interplay in PD neurodegeneration.
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Registered trials
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 Socratic graph.