ArticleJournal of neuroinflammation2019
Leucine-rich repeat kinase-2 (LRRK2) modulates paraquat-induced inflammatory sickness and stress phenotype.
Article in Journal of neuroinflammation, 2019. 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
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Chronic Paraquat Neurotoxicity and Dopaminergic Degeneration: A Mechanistic Review.Chemistry & biodiversity · 2026Review
- LRRK2 as a Potential Disease-Modifying Target in Sporadic Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Review
- Drug discovery and development for Parkinson's disease: are preclinical models good enough?Frontiers in aging neuroscience · 2025Review
- Selective dopaminergic neurotoxicity modulated by inherent cell-type specific neurobiology.Neurotoxicology · 2024Review
- LRRK2 kinase inhibition protects against Parkinson's disease-associated environmental toxicants.Neurobiology of disease · 2024Article
- Genetic variation and pesticide exposure influence blood DNA methylation signatures in females with early-stage Parkinson's disease.NPJ Parkinson's disease · 2024Article
- The Body, the Brain, the Environment, and Parkinson's Disease.Journal of Parkinson's disease · 2024Review
- Occupational Pesticide Exposure in Parkinson's Disease Related to GBA and LRRK2 Variants.Journal of Parkinson's disease · 2024Article
- LRRK2 G2019S promotes astrocytic inflammation induced by oligomeric α-synuclein through NF-κB pathway.iScience · 2023Article
- Pesticides and the Microbiome-Gut-Brain Axis: Convergent Pathways in the Pathogenesis of Parkinson's Disease.Journal of Parkinson's disease · 2023Review
- Environmental Impact on the Epigenetic Mechanisms Underlying Parkinson's Disease Pathogenesis: A Narrative Review.Brain sciences · 2022Review
- DNA methylation as a mediator of genetic and environmental influences on Parkinson's disease susceptibility: Impacts of alpha-Synuclein, physical activity, and pesticide exposure on the epigenome.Frontiers in genetics · 2022Review
- Preventing Parkinson's Disease: An Environmental Agenda.Journal of Parkinson's disease · 2022Review
- In silico comparative analysis of LRRK2 interactomes from brain, kidney and lung.Brain research · 2021Article
- The industrial solvent trichloroethylene induces LRRK2 kinase activity and dopaminergic neurodegeneration in a rat model of Parkinson's disease.Neurobiology of disease · 2021Article
- Genetic and Environmental Factors Influence the Pleomorphy ofInternational journal of molecular sciences · 2021Review
- The impact of dextran sodium sulphate and probiotic pre-treatment in a murine model of Parkinson's disease.Journal of neuroinflammation · 2021Article
- Inhibitory effect of pirfenidone on pulmonary fibrosis in patients with acute paraquat poisoning.American journal of translational research · 2021Article
- Microglia depletion prior to lipopolysaccharide and paraquat treatment differentially modulates behavioral and neuronal outcomes in wild type and G2019S LRRK2 knock-in mice.Brain, behavior, & immunity - health · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLeucine-rich repeat kinase 2 (LRRK2) is a common gene implicated in Parkinson's disease (PD) and is also thought to be fundamentally involved in numerous immune functions. Thus, we assessed the role of LRRK2 in the context of the effects of the environmental toxicant, paraquat, that has been implicated in PD and is known to affect inflammatory processes.
methodsMale LRRK2 knockout (KO) and transgenic mice bearing the G2019S LRRK2 mutation (aged 6-8 months) or their littermate controls were exposed to paraquat (two times per week for 3 weeks), and sickness measures, motivational scores, and total home-cage activity levels were assessed. Following sacrifice, western blot and ELISA assays were performed to see whether or not LRRK2 expression would alter processes related to plasticity, immune response processes, or the stress response.
resultsParaquat-induced signs of sickness, inflammation (elevated IL-6), and peripheral toxicity (e.g., organ weight) were completely prevented by LRRK2 knockout. In fact, LRRK2 knockout dramatically reduced not only signs of illness, but also the motivational (nest building) and home-cage activity deficits induced by paraquat. Although LRRK2 deficiency did not affect the striatal BDNF reduction that was provoked by paraquat, it did blunt the corticosterone elevation induced by paraquat, raising the possibility that LRRK2 may modulate aspects of the HPA stress axis. Accordingly, we found that transgenic mice bearing the G2019S LRRK2 mutation had elevated basal corticosterone, along with diminished hippocampal 5-HT1A levels.
conclusionWe are the first to show the importance of LRRK2 in the peripheral neurotoxic and stressor-like effects of paraquat. These data are consistent with LRRK2 playing a role in the general inflammatory tone and stressor effects induced by environmental toxicant exposure.
Indexed as
Identifiers
What OpenQuestion holds
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.