ArticleNPJ Parkinson's disease2022
Effect of LRRK2 protein and activity on stimulated cytokines in human monocytes and macrophages.
Article in NPJ Parkinson's disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 40 citations in OpenAlex.
- Profiling peripheral immune cells in Parkinson's disease: A scoping review.Journal of Parkinson's disease · 2026Review
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- Colonic LRRK2 expression is increased in Crohn's disease but not in Parkinson's disease and idiopathic RBD.Acta neuropathologica · 2026Article
- Parabacteroides goldsteinii mitigates parkinsonism in LRRK2 mutant mice by reducing neuroinflammation through Gut-Brain axis.Journal of advanced research · 2026Article
- The Parkinson's disease-linked G2019S mutation of LRRK2 increases NADPH oxidase-2 activity in neutrophils for superior control of bacterial infections.Cellular & molecular immunology · 2026Article
- Article
- miR-369-3p Modulates LRRK2-Mediated Inflammation and Autophagy in RAW264.7 Macrophages.International journal of molecular sciences · 2026Article
- LRRK2 kinase mediates increased GCase activity in microglia in response to IFNγ-induced proinflammatory stimulation.NPJ Parkinson's disease · 2026Article
- Parkinson's-Linked LRRK2 and GBA1 Mutations Modulate the Peripheral Immune Response to Pseudomonas aeruginosa.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- LRRK2NPJ Parkinson's disease · 2026Article
- Investigating the therapeutic mechanism of Puerarin in vascular dementia: an integrated approach combining network pharmacology and experimental validation.Frontiers in pharmacology · 2026Article
- LRRK2 G2019S reprograms innate and adaptive immunity to drive context-dependent host defense outcomes.Frontiers in cellular neuroscience · 2026Article
- Interferon gamma stimulates coordinated changes in LRRK2, GCase, and cathepsin activities in idiopathic and genetic Parkinson's disease monocytes.NPJ Parkinson's disease · 2025Article
- Oligomeric alpha-synuclein causes early synaptic dysfunction of the corticostriatal pathway associated with non-motor symptoms.NPJ Parkinson's disease · 2025Article
- Inflammation and IL-4 regulate Parkinson's and Crohn's disease associated kinase LRRK2.EMBO reports · 2025Article
- LRRK2 in Drosophila Melanogaster Model: Insights into Cellular Dysfunction and Neuroinflammation in Parkinson's Disease.International journal of molecular sciences · 2025Review
- Exploring LRRK2-dependent Mechanisms in Parkinson's Disease Therapy.CNS & neurological disorders drug targets · 2025Review
- The design and development of LRRK2 inhibitors as novel therapeutics for Parkinson's disease.Future medicinal chemistry · 2025Review
- Modeling Parkinson's disease pathology in human dopaminergic neurons by sequential exposure to α-synuclein fibrils and proinflammatory cytokines.Nature neuroscience · 2024Article
- The Gut Microbiota Involvement in the Panorama of Muscular Dystrophy Pathogenesis.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Leucine-rich-repeat kinase 2 (LRRK2), a potential therapeutic target for the treatment of Parkinson's disease (PD), is highly expressed in monocytes and macrophages and may play a role in the regulation of inflammatory pathways. To determine how LRRK2 protein levels and/or its activity modulate inflammatory cytokine/chemokine levels in human immune cells, isogenic human induced pluripotent stem cells (iPSC) with the LRRK2-activating G2019S mutation, wild-type LRRK2, and iPSC deficient in LRRK2 were differentiated to monocytes and macrophages and stimulated with inflammatory toll-like receptor (TLR) agonists in the presence and absence of LRRK2 kinase inhibitors. The effect of LRRK2 inhibitors and the effect of increasing LRRK2 levels with interferon gamma on TLR-stimulated cytokines were also assessed in primary peripheral blood-derived monocytes. Monocytes and macrophages with the LRRK2 G2019S mutation had significantly higher levels of cytokines and chemokines in tissue culture media following stimulation with TLR agonists compared to isogenic controls. Knockout of LRRK2 impaired phagocytosis but did not significantly affect TLR-mediated cytokine levels. Interferon gamma significantly increased the levels of LRRK2 and phosphorylation of its downstream Rab10 substrate, and potentiated TLR-mediated cytokine levels. LRRK2 kinase inhibitors did not have a major effect on TLR-stimulated cytokine levels. Results suggest that the LRRK2 G2019S mutation may potentiate inflammation following activation of TLRs. However, this was not dependent on LRRK2 kinase activity. Indeed, LRRK2 kinase inhibitors had little effect on TLR-mediated inflammation under the conditions employed in this study.
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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.