ArticlePLoS genetics2010
Extracellular dopamine potentiates mn-induced oxidative stress, lifespan reduction, and dopaminergic neurodegeneration in a BLI-3-dependent manner in Caenorhabditis elegans.
Article in PLoS genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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99 citing papers in PubMed, 197 citations in OpenAlex.
- Emergent latent neurotoxic effects of manganese following nominal chronic exposures in human stem cell and Caenorhabditis elegans models.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Alpha-methyl-para-tyrosine and amphetamine ameliorate hyperactivity in a novel mouse model of dopamine transporter deficiency syndrome.EMBO molecular medicine · 2026Article
- Combined metallomics and metabolomics reveal impact of metal homeostasis on biological pathways in C. elegans.Analytical and bioanalytical chemistry · 2026Article
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- Lithium nickel manganese cobalt oxide particles cause developmental neurotoxicity inEnvironmental science. Advances · 2025Article
- The Inhibition of Fatty Acid Amide Hydrolase-4 Affords Neuroprotection in a Toxic Model Induced by 6-Hydroxydopamine in Caenorhabditis elegans Nematodes.Molecular neurobiology · 2025Article
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- Consensus of Expert Opinion for the Diagnosis and Management of Hypermanganesaemia With Dystonia 1 and 2.Journal of inherited metabolic disease · 2025Article
- Stage-specific exposure of Caenorhabditis elegans to cadmium identifies unique transcriptomic response cascades and an uncharacterized cadmium responsive transcript.Metallomics : integrated biometal science · 2024Article
- Consequences of Disturbing Manganese Homeostasis.International journal of molecular sciences · 2023Review
- Identification of the bacterial metabolite aerugine as potential trigger of human dopaminergic neurodegeneration.Environment international · 2023Article
- Dopaminergic modulation by quercetin: In silico and in vivo evidence using Caenorhabditis elegans as a model.Chemico-biological interactions · 2023Article
- The Role of Oxidative Stress in Manganese Neurotoxicity: A Literature Review Focused on Contributions Made by Professor Michael Aschner.Biomolecules · 2023Review
- Casein kinase 1 gamma regulates oxidative stress response via interacting with the NADPH dual oxidase complex.PLoS genetics · 2023Article
- An unbiased, automated platform for scoring dopaminergic neurodegeneration inbioRxiv : the preprint server for biology · 2023Article
- Neurotoxicology of metals and metallic nanoparticles inAdvances in neurotoxicology · 2023Article
- An unbiased, automated platform for scoring dopaminergic neurodegeneration in C. elegans.PloS one · 2023Article
- Article
- Review
- BTBD9 attenuates manganese-induced oxidative stress and neurotoxicity by regulating insulin growth factor signaling pathway.Human molecular genetics · 2022Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Parkinson's disease (PD)-mimicking drugs and pesticides, and more recently PD-associated gene mutations, have been studied in cell cultures and mammalian models to decipher the molecular basis of PD. Thus far, a dozen of genes have been identified that are responsible for inherited PD. However they only account for about 8% of PD cases, most of the cases likely involving environmental contributions. Environmental manganese (Mn) exposure represents an established risk factor for PD occurrence, and both PD and Mn-intoxicated patients display a characteristic extrapyramidal syndrome primarily involving dopaminergic (DAergic) neurodegeneration with shared common molecular mechanisms. To better understand the specificity of DAergic neurodegeneration, we studied Mn toxicity in vivo in Caenorhabditis elegans. Combining genetics and biochemical assays, we established that extracellular, and not intracellular, dopamine (DA) is responsible for Mn-induced DAergic neurodegeneration and that this process (1) requires functional DA-reuptake transporter (DAT-1) and (2) is associated with oxidative stress and lifespan reduction. Overexpression of the anti-oxidant transcription factor, SKN-1, affords protection against Mn toxicity, while the DA-dependency of Mn toxicity requires the NADPH dual-oxidase BLI-3. These results suggest that in vivo BLI-3 activity promotes the conversion of extracellular DA into toxic reactive species, which, in turn, can be taken up by DAT-1 in DAergic neurons, thus leading to oxidative stress and cell degeneration.
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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 OpenQuestion graph.