ArticleHuman molecular genetics2015
The G2019S LRRK2 mutation increases myeloid cell chemotactic responses and enhances LRRK2 binding to actin-regulatory proteins.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 75 citations in OpenAlex.
- 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
- Peripheral immunochemical considerations in Parkinson disease: sources, targets and crosstalk mechanisms.Journal of translational medicine · 2026Review
- Tissue-specific transcriptional epistasis between Prkn and Lrrk2 during mycobacterial infection.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- Intestinal inflammation promotes neuroinflammation and PD-associated nigrostriatal pathology independently of LRRK2 G2019S kinase activity.Frontiers in cellular neuroscience · 2026Article
- Lrrk2 G2019S mutation incites increased cell-intrinsic neutrophil effector functions and intestinal inflammation in a model of infectious colitis.NPJ Parkinson's disease · 2025Article
- Loss of LRRK2 activity induces cytoskeleton defects and oxidative stress during porcine oocyte maturation.Cell communication and signaling : CCS · 2025Article
- Article
- Multiple sclerosis inFrontiers in neurology · 2024Article
- Formation of templated inclusions in a forebrain α-synuclein mouse model is independent of LRRK2.Neurobiology of disease · 2023Article
- LRRK2 suppresses lysosome degradative activity in macrophages and microglia through MiT-TFE transcription factor inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Mutant LRRK2 exacerbates immune response and neurodegeneration in a chronic model of experimental colitis.Acta neuropathologica · 2023Article
- The interplay between monocytes, α-synuclein and LRRK2 in Parkinson's disease.Biochemical Society transactions · 2023Review
- Immunological Features of LRRK2 Function and Its Role in the Gut-Brain Axis Governing Parkinson's Disease.Journal of Parkinson's disease · 2023Review
- FTIR Characterization of Sulfated Polysaccharides Obtained fromMarine drugs · 2022Article
- α2,6 Sialylation mediated by ST6GAL1 promotes glioblastoma growth.JCI insight · 2022Article
- Mitochondrial ROS promotes susceptibility to infection via gasdermin D-mediated necroptosis.Cell · 2022Article
- Elevated Urinary Rab10 Phosphorylation in Idiopathic Parkinson Disease.Movement disorders : official journal of the Movement Disorder Society · 2022Article
- Exploring the focal role of LRRK2 kinase in Parkinson's disease.Environmental science and pollution research international · 2022Review
- LRRK2 regulates actin assembly for spindle migration and mitochondrial function in mouse oocyte meiosis.Journal of molecular cell biology · 2022Article
- Pathological α-synuclein recruits LRRK2 expressing pro-inflammatory monocytes to the brain.Molecular neurodegeneration · 2022Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The Leucine rich repeat kinase 2 (LRRK2) gene is genetically and biochemically linked to several diseases that involve innate immunity. LRRK2 protein is highly expressed in phagocytic cells of the innate immune system, most notably in myeloid cells capable of mounting potent pro-inflammatory responses. Knockdown of LRRK2 protein in these cells reduces pro-inflammatory responses. However, the effect of LRRK2 pathogenic mutations that cause Parkinson's disease on myeloid cell function is not clear but could provide insight into LRRK2-linked disease. Here, we find that rats expressing G2019S LRRK2 have exaggerated pro-inflammatory responses and subsequent neurodegeneration after lipopolysaccharide injections in the substantia nigra, with a marked increase in the recruitment of CD68 myeloid cells to the site of injection. While G2019S LRRK2 expression did not affect immunological homeostasis, myeloid cells expressing G2019S LRRK2 show enhanced chemotaxis both in vitro in two-chamber assays and in vivo in response to thioglycollate injections in the peritoneum. The G2019S mutation enhanced the association between LRRK2 and actin-regulatory proteins that control chemotaxis. The interaction between G2019S LRRK2 and actin-regulatory proteins can be blocked by LRRK2 kinase inhibitors, although we did not find evidence that LRRK2 phosphorylated these interacting proteins. These results suggest that the primary mechanism of G2019S LRRK2 with respect to myeloid cell function in disease may be related to exaggerated chemotactic responses.
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