ArticleToxicology2014
Rotenone and paraquat perturb dopamine metabolism: A computational analysis of pesticide toxicity.
Article in Toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
19 citing papers in PubMed, 52 citations in OpenAlex.
- CAD (Cath. a-Differentiated) Cells Produce Dopamine along with Dopamine-Synthesizing Enzymes.Neurochemical research · 2025Article
- Comparison of the effect of rotenone and 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine on inducing chronic Parkinson's disease in mouse models.Molecular medicine reports · 2022Article
- Role of neurotoxicants in the pathogenesis of Alzheimer's disease: a mechanistic insight.Annals of medicine · 2021Review
- Parkinson's disease: Alterations in iron and redox biology as a key to unlock therapeutic strategies.Redox biology · 2021Review
- Role of environmental pollutants in Alzheimer's disease: a review.Environmental science and pollution research international · 2020Review
- Acquired dysregulation of dopamine homeostasis reproduces features of Parkinson's disease.NPJ Parkinson's disease · 2020Article
- A Review on Occurrence of Pesticides in Environment and Current Technologies for Their Remediation and Management.Indian journal of microbiology · 2020Review
- The Role of Xenobiotics and Trace Metals in Parkinson's Disease.Molecular neurobiology · 2020Review
- Associations between atherosclerosis and neurological diseases, beyond ischemia-induced cerebral damage.Reviews in endocrine & metabolic disorders · 2019Review
- Mathematical Biology Models of Parkinson's Disease.CPT: pharmacometrics & systems pharmacology · 2019Review
- Prevention of progression in Parkinson's disease.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2018Review
- The Exposome Paradigm in Human Health: Lessons from the Emory Exposome Summer Course.Environmental health perspectives · 2017Article
- Inference of cancer mechanisms through computational systems analysis.Molecular bioSystems · 2017Article
- A knowledge-based approach for predicting gene-disease associations.Bioinformatics (Oxford, England) · 2016Article
- Neuroprotective Effects of a Standardized Flavonoid Extract from Safflower against a Rotenone-Induced Rat Model of Parkinson's Disease.Molecules (Basel, Switzerland) · 2016Article
- SUR1 Receptor Interaction with Hesperidin and Linarin Predicts Possible Mechanisms of Action of Valeriana officinalis in Parkinson.Frontiers in aging neuroscience · 2016Article
- Role of environmental contaminants in the etiology of Alzheimer's disease: a review.Current Alzheimer research · 2015Review
- Identification of cancer mechanisms through computational systems modeling.Translational cancer research · 2014Article
- Strategies for Comparing Metabolic Profiles: Implications for the Inference of Biochemical Mechanisms from Metabolomics Data.IEEE/ACM transactions on computational biology and bioinformaticsArticle
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Pesticides, such as rotenone and paraquat, are suspected in the pathogenesis of Parkinson's disease (PD), whose hallmark is the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Thus, compounds expected to play a role in the pathogenesis of PD will likely impact the function of dopaminergic neurons. To explore the relationship between pesticide exposure and dopaminergic toxicity, we developed a custom-tailored mathematical model of dopamine metabolism and utilized it to infer potential mechanisms underlying the toxicity of rotenone and paraquat, asking how these pesticides perturb specific processes. We performed two types of analyses, which are conceptually different and complement each other. The first analysis, a purely algebraic reverse engineering approach, analytically and deterministically computes the altered profile of enzyme activities that characterize the effects of a pesticide. The second method consists of large-scale Monte Carlo simulations that statistically reveal possible mechanisms of pesticides. The results from the reverse engineering approach show that rotenone and paraquat exposures lead to distinctly different flux perturbations. Rotenone seems to affect all fluxes associated with dopamine compartmentalization, whereas paraquat exposure perturbs fluxes associated with dopamine and its breakdown metabolites. The statistical results of the Monte-Carlo analysis suggest several specific mechanisms. The findings are interesting, because no a priori assumptions are made regarding specific pesticide actions, and all parameters characterizing the processes in the dopamine model are treated in an unbiased manner. Our results show how approaches from computational systems biology can help identify mechanisms underlying the toxicity of pesticide exposure.
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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.