ArticleNeurobiology of disease2021
The industrial solvent trichloroethylene induces LRRK2 kinase activity and dopaminergic neurodegeneration in a rat model of Parkinson's disease.
Article in Neurobiology of disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 67 citations in OpenAlex.
- Addressing the Challenges of Translating LRRK2 Biology into Disease-Modifying Therapies: The LRRK2 Investigative Therapeutics Exchange Initiative.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Knockout of the LRRK2-counteracting RAB phosphatase PPM1H disrupts axonal autophagy and exacerbates alpha-synuclein aggregation.Cell reports · 2026Article
- Article
- Preventing Parkinson's disease in the context of movement disorders: a narrative review of current evidence and future directions.Neurological research and practice · 2026Review
- Neurodegeneration in Parkinson's Disease: The Role of Environmental Toxins.Journal of central nervous system disease · 2026Review
- A PLAN to address the Parkinson pandemic.Journal of Parkinson's disease · 2025Review
- Trichloroethylene Exposure and Parkinson's Disease: Environmental Risk, Metabolic Pathways, and Mechanistic Insights.Molecular neurobiology · 2025Review
- LRRK2 integrates Rab and GABARAP interactions to sense and respond to distinct lysosomal stresses.bioRxiv : the preprint server for biology · 2025Article
- Environmental toxins in neurodegeneration - a narrative review.Neurological research and practice · 2025Review
- Ambient Trichloroethylene Exposure and Parkinson Disease Risk in Medicare Beneficiaries.Neurology · 2025Article
- LRRK2-mediated mitochondrial dysfunction in Parkinson's disease.The Biochemical journal · 2025Review
- Environmental Risk Factors for Parkinson's Disease: A Critical Review and Policy Implications.Movement disorders : official journal of the Movement Disorder Society · 2025Review
- Declining trends in the incidence of Parkinson's disease: A cohort study in Germany.Journal of Parkinson's disease · 2025Article
- Parkinson's disease physiopathology-beyond theFrontiers in aging neuroscience · 2025Review
- Trichloroethylene: An Update on an Environmental Contaminant with Multiple Health Effects.Annual review of pharmacology and toxicology · 2025Review
- Parkinson's Disease Progression and Exposure to Contaminated Water at Camp Lejeune.Movement disorders : official journal of the Movement Disorder Society · 2024Article
- Update: Protective and risk factors for Parkinson disease.Parkinsonism & related disorders · 2024Review
- Microglial Sp1 induced LRRK2 upregulation in response to manganese exposure, and 17β-estradiol afforded protection against this manganese toxicity.Neurotoxicology · 2024Article
- Neurotoxicology of dopamine: Victim or assailant?Neurotoxicology · 2024Review
- LRRK2 kinase inhibition protects against Parkinson's disease-associated environmental toxicants.Neurobiology of disease · 2024Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Gene-environment interaction is implicated in the majority of idiopathic Parkinson's disease (PD) risk, and some of the most widespread environmental contaminants are selectively toxic to dopaminergic neurons. Pesticides have long been connected to PD incidence, however, it has become increasingly apparent that other industrial byproducts likely influence neurodegeneration. For example, organic solvents, which are used in chemical, machining, and dry-cleaning industries, are of growing concern, as decades of solvent use and their effluence into the environment has contaminated much of the world's groundwater and soil. Like some pesticides, certain organic solvents, such as the chlorinated halocarbon trichloroethylene (TCE), are mitochondrial toxicants, which are collectively implicated in the pathogenesis of dopaminergic neurodegeneration. Recently, we hypothesized a possible gene-environment interaction may occur between environmental mitochondrial toxicants and the protein kinase LRRK2, mutations of which are the most common genetic cause of familial and sporadic PD. In addition, emerging data suggests that elevated wildtype LRRK2 kinase activity also contributes to the pathogenesis of idiopathic PD. To this end, we investigated whether chronic, systemic TCE exposure (200 mg/kg) in aged rats produced wildtype LRRK2 activation and caused nigrostriatal dopaminergic dysfunction. Interestingly, we found that TCE not only induced LRRK2 kinase activity in the brain, but produced a significant dopaminergic lesion in the nigrostriatal tract, elevated oxidative stress, and caused endolysosomal dysfunction and α-synuclein accumulation. Together, these data suggest that TCE-induced LRRK2 kinase activity contributed to the selective toxicity of dopaminergic neurons. We conclude that gene-environment interactions between certain industrial contaminants and LRRK2 likely influence PD risk.
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