ArticleNature communications2015
LRRK2 G2019S mutation attenuates microglial motility by inhibiting focal adhesion kinase.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 114 citations in OpenAlex.
- Leucine-rich repeat kinase 2 (LRRK2): balancing cellular homeostasis and Parkinson's disease (PD) pathogenesis.Annals of medicine · 2026Review
- Generation of Leucine-Rich Repeat Kinase 2 (LRRK2) Knockout Neuroblastoma Cells SH-SY5Y by CRISPR/Cas9-Mediated Genome Editing.Biochemical genetics · 2026Article
- The emerging role and therapeutic targeting of autophagy-lysosome pathway in the pathogenesis of Parkinson's disease.Translational neurodegeneration · 2026Review
- Peripheral immunochemical considerations in Parkinson disease: sources, targets and crosstalk mechanisms.Journal of translational medicine · 2026Review
- LRRK2-mutant microglia and neuromelanin synergize to drive dopaminergic neurodegeneration in an iPSC-based Parkinson's disease model.Communications biology · 2025Article
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- Astrocytic and microglial cell functions in neuroinflammatory diseases and their animal models.Frontiers in cellular neuroscience · 2025Review
- Molecular and spatial transcriptomic classification of midbrain dopamine neurons and their alterations in a LRRK2bioRxiv : the preprint server for biology · 2024Article
- Deficiency of leucine-rich repeat kinase 2 aggravates thioacetamide-induced acute liver failure and hepatic encephalopathy in mice.Journal of neuroinflammation · 2024Article
- Expression of G2019S LRRK2 in Rat Primary Astrocytes Mediates Neurotoxicity and Alters the Dopamine Synthesis Pathway in N27 Cells via Astrocytic Proinflammatory Cytokines and Neurotrophic Factors.Current issues in molecular biology · 2024Article
- Integration of iPSC-Derived Microglia into Brain Organoids for Neurological Research.International journal of molecular sciences · 2024Review
- Microglia: roles and genetic risk in Parkinson's disease.Frontiers in neuroscience · 2024Review
- How Parkinson's Disease-Linked LRRK2 Mutations Affect Different CNS Cell Types.Journal of Parkinson's disease · 2024Review
- LRRK2 G2019S promotes astrocytic inflammation induced by oligomeric α-synuclein through NF-κB pathway.iScience · 2023Article
- Longitudinal dysregulation of long non-coding RNAs in Parkinson's disease.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- LRRK2 Gly2019Ser Mutation Promotes ER Stress via Interacting with THBS1/TGF-β1 in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The Involvement of Neuroinflammation in the Onset and Progression of Parkinson's Disease.International journal of molecular sciences · 2023Review
- The contribution of inflammatory astrocytes to BBB impairments in a brain-chip model of Parkinson's disease.Nature communications · 2023Article
- The Integrin Pathway Partially Mediates Stretch-Induced Deficits in Primary Rat Microglia.Molecular neurobiology · 2023Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In response to brain injury, microglia rapidly extend processes that isolate lesion sites and protect the brain from further injury. Here we report that microglia carrying a pathogenic mutation in the Parkinson's disease (PD)-associated gene, G2019S-LRRK2 (GS-Tg microglia), show retarded ADP-induced motility and delayed isolation of injury, compared with non-Tg microglia. Conversely, LRRK2 knockdown microglia are highly motile compared with control cells. In our functional assays, LRRK2 binds to focal adhesion kinase (FAK) and phosphorylates its Thr-X-Arg/Lys (TXR/K) motif(s), eventually attenuating FAK activity marked by decreased pY397 phosphorylation (pY397). GS-LRRK2 decreases the levels of pY397 in the brain, microglia and HEK cells. In addition, treatment with an inhibitor of LRRK2 kinase restores pY397 levels, decreased pTXR levels and rescued motility of GS-Tg microglia. These results collectively suggest that G2019S mutation of LRRK2 may contribute to the development of PD by inhibiting microglial response to brain injury.
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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.