ArticleNeurobiology of disease2019
Transcriptome analysis of LRRK2 knock-out microglia cells reveals alterations of inflammatory- and oxidative stress-related pathways upon treatment with α-synuclein fibrils.
Article in Neurobiology of disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Molecular Pathways Involved in LRRK2-Linked Parkinson's Disease: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Mosaic: Single-Cell Atlas of Stress.Cells · 2026Review
- LRRK2-Mediated Neuroinflammation-Induced Neuronal Dysfunctions in a Parkinson's and Alzheimer's Disease Cellular Model.Biomolecules · 2025Article
- Recent advances in targeting LRRK2 for Parkinson's disease treatment.Journal of translational medicine · 2025Review
- Multitissue single-cell analysis reveals differential cellular and molecular sensitivity between fructose and high-fat high-sucrose diets.Cell reports · 2025Article
- 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
- LRRK2 in Drosophila Melanogaster Model: Insights into Cellular Dysfunction and Neuroinflammation in Parkinson's Disease.International journal of molecular sciences · 2025Review
- Inhibition of LRRK2 Ameliorates Aspergillus fumigatus Keratitis by Regulating STING Signaling Pathways.Investigative ophthalmology & visual science · 2025Article
- The immune system in Parkinson's disease: what we know so far.Brain : a journal of neurology · 2024Review
- Pressure sensing of lysosomes enables control of TFEB responses in macrophages.Nature cell biology · 2024Article
- Evaluation of Neuroinflammatory Contribution to Neurodegeneration in LRRK2Biomedicines · 2024Article
- A Comprehensive Approach to Parkinson's Disease: Addressing Its Molecular, Clinical, and Therapeutic Aspects.International journal of molecular sciences · 2024Review
- Reactive oxygen species-scavenging nanomaterials for the prevention and treatment of age-related diseases.Journal of nanobiotechnology · 2024Review
- Deficiency of leucine-rich repeat kinase 2 aggravates thioacetamide-induced acute liver failure and hepatic encephalopathy in mice.Journal of neuroinflammation · 2024Article
- Article
- Overlapping Neuroimmune Mechanisms and Therapeutic Targets in Neurodegenerative Disorders.Biomedicines · 2023Review
- The Involvement of Neuroinflammation in the Onset and Progression of Parkinson's Disease.International journal of molecular sciences · 2023Review
- Article
- Allele-dependent interaction of LRRK2 and NOD2 in leprosy.PLoS pathogens · 2023Article
- LRRK2 Kinase Inhibition Attenuates Astrocytic Activation in Response to Amyloid βBiomolecules · 2023Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Several previous studies have linked the Parkinson's disease (PD) gene LRRK2 to the biology of microglia cells. However, the precise ways in which LRRK2 affects microglial function have not been fully resolved. Here, we used the RNA-Sequencing to obtain transcriptomic profiles of LRRK2 wild-type (WT) and knock-out (KO) microglia cells treated with α-synuclein pre-formed fibrils (PFFs) or lipopolysaccharide (LPS) as a general inflammatory insult. We observed that, although α-synuclein PFFs and LPS mediate overlapping gene expression profiles in microglia, there are also distinct responses to each stimulus. α-Synuclein PFFs trigger alterations of oxidative stress-related pathways with the mitochondrial dismutase Sod2 as a strongly differentially regulated gene. We validated SOD2 at mRNA and protein levels. Furthermore, we found that LRRK2 KO microglia cells reported attenuated induction of mitochondrial SOD2 in response to α-synuclein PFFs, indicating a potential contribution of LRRK2 to oxidative stress-related pathways. We validate several genes in vivo using single-cell RNA-Seq from acutely isolated microglia after striatal injection of LPS into the mouse brain. Overall, these results suggest that microglial LRRK2 may contribute to the pathogenesis of PD via altered oxidative stress signaling.
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Registered trials
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