ArticleJournal of neuroinflammation2015
Leucine-rich repeat kinase 2 positively regulates inflammation and down-regulates NF-κB p50 signaling in cultured microglia cells.
Article in Journal of neuroinflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 130 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
- Leucine-Rich Repeat Kinase 2 (LRRK2) in Glucose Metabolism and Metabolic-Neuroinflammatory Crosstalk.Biomolecules · 2026Review
- Mechanistic of LRRK2-Mediated Pyroptosis Via the NLRP3/Caspase-1/GSDMD Pathway in Parkinson's Disease Progression.Inflammation · 2026Article
- LRRK2 mediates haloperidol-induced changes in indirect pathway striatal projection neurons.Molecular psychiatry · 2025Article
- LRRK2-Mediated Neuroinflammation-Induced Neuronal Dysfunctions in a Parkinson's and Alzheimer's Disease Cellular Model.Biomolecules · 2025Article
- An update on the involvement of inflammatory mediators in Parkinson's disease pathogenesis.Archives of toxicology · 2025Review
- Biomarkers and therapeutic strategies targeting microglia in neurodegenerative diseases: current status and future directions.Molecular neurodegeneration · 2025Review
- Recent advances in targeting LRRK2 for Parkinson's disease treatment.Journal of translational medicine · 2025Review
- Astrocytes carrying LRRK2 G2019S exhibit increased levels of clusterin chaperone via miR-22-5p and reduced ability to take up α-synuclein fibrils.Acta neuropathologica communications · 2025Article
- The Multifaceted Role of LRRK2 in Parkinson's Disease.Brain sciences · 2025Review
- 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
- Neuroinflammatory mechanisms may help identify candidate biomarkers in chronic traumatic encephalopathy (CTE).Free neuropathology · 2025Review
- Inhibition of Protease-Activated Receptor-2 Activation in Parkinson's Disease Using 1-Piperidin Propionic Acid.Biomedicines · 2024Article
- Deficiency of leucine-rich repeat kinase 2 aggravates thioacetamide-induced acute liver failure and hepatic encephalopathy in mice.Journal of neuroinflammation · 2024Article
- LRRK2; Communicative Role in the Treatment of Parkinson's Disease and Ulcerative Colitis Overlapping.CNS & neurological disorders drug targets · 2024Review
- Article
- LRRK2 G2019S promotes astrocytic inflammation induced by oligomeric α-synuclein through NF-κB pathway.iScience · 2023Article
- Overlapping Neuroimmune Mechanisms and Therapeutic Targets in Neurodegenerative Disorders.Biomedicines · 2023Review
- Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets.Signal transduction and targeted therapy · 2023Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 1 institution in 3 countries.
Funding
Abstract
backgroundOver-activated microglia and chronic neuroinflammation contribute to dopaminergic neuron degeneration and progression of Parkinson's disease (PD). Leucine-rich repeat kinase 2 (LRRK2), a kinase mutated in autosomal dominantly inherited and sporadic PD cases, is highly expressed in immune cells, in which it regulates inflammation through a yet unclear mechanism.
methodsHere, using pharmacological inhibition and cultured Lrrk2 (-/-) primary microglia cells, we validated LRRK2 as a positive modulator of inflammation and we investigated its specific function in microglia cells.
resultsInhibition or genetic deletion of LRRK2 causes reduction of interleukin-1β and cyclooxygenase-2 expression upon lipopolysaccharide-mediated inflammation. LRRK2 also takes part of the signaling trigged by α-synuclein fibrils, which culminates in induction of inflammatory mediators. At the molecular level, loss of LRRK2 or inhibition of its kinase activity results in increased phosphorylation of nuclear factor kappa-B (NF-κB) inhibitory subunit p50 at S337, a protein kinase A (PKA)-specific phosphorylation site, with consequent accumulation of p50 in the nucleus.
conclusionsTaken together, these findings point to a role of LRRK2 in microglia activation and sustainment of neuroinflammation and in controlling of NF-κB p50 inhibitory signaling. Understanding the molecular pathways coordinated by LRRK2 in activated microglia cells after pathological stimuli such us fibrillar α-synuclein holds the potential to provide novel targets for PD therapeutics.
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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.