ArticleNature communications2020
Interferon-γ signaling synergizes with LRRK2 in neurons and microglia derived from human induced pluripotent stem cells.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 131 citations in OpenAlex.
- From wheal to wellness: efficacy and safety of ligelizumab in chronic spontaneous urticaria: a systematic review and meta-analysis.Archives of dermatological research · 2025Pooled it
- Modeling human neurodegeneration with iPSCs: opportunities, limitations, and the challenge of aging.The Journal of clinical investigation · 2026Review
- The mitochondrial unfolded protein response in human microglia disrupts neuronal-glial communication and promotes senescence.Nature neuroscience · 2026Article
- The LRRK2 G2019S variant rewires Rab GTPase phosphorylation after lysosomal damage and promotes cell death in human macrophages.Journal of cell science · 2026Article
- Calcineurin/NFAT signaling in the temporal integration of Ca²⁺ stress in neurodegeneration.Cell death discovery · 2026Review
- TNF-α induces type I IFN signalling to suppress neurogenesis and recruit T cells.Nature communications · 2026Article
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- 1 Hz Low-Frequency Repetitive Transcranial Magnetic Stimulation Ameliorates Epilepsy by Suppressing Interferon-γ Signaling-Dependent Microglial Synaptic Phagocytosis in Mice.CNS neuroscience & therapeutics · 2026Article
- Using iPSC models to examine neuron-glia interactions in neurodegenerative diseases.Bioscience reports · 2026Review
- Dissecting microglial contributions to neurodegenerative disease pathophysiology using human pluripotent stem cells.Stem cell reports · 2026Review
- Parkinson's Disease Patient-Specific Striatum Organoids Show Hallmarks of Increased Inflammation.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Inflammatory signaling differentially changes chromatin accessibility and gene expression of the PD- associated kinase LRRK2 between human and mice.Molecular neurodegeneration · 2026Article
- The Interferon-miR-146a-5p-Stat1/Nrf2 Pathway Mediates LRRK2-R1441G-induced M1 over M2 Microglia Activation.Molecular neurobiology · 2026Article
- LRRK2 kinase mediates increased GCase activity in microglia in response to IFNγ-induced proinflammatory stimulation.NPJ Parkinson's disease · 2026Article
- Role of LRRK2 in physiological activities, diseases, and therapy.Chinese medical journal · 2026Review
- Inflammatory signaling differentially changes chromatin accessibility and gene expression of the PD- associated kinase LRRK2 between human and mice.bioRxiv : the preprint server for biology · 2026Article
- Metabolic reprogramming and altered ATP content impair neuroprotective functions of microglia in β-glucocerebrosidase deficiency models.Journal of neuroinflammation · 2025Article
- Redirecting microglia phenotype via inhibition of NFAT1 ameliorates deficits in mouse model of synucleinopathies.Experimental & molecular medicine · 2025Article
- The Parkinson's disease-associated LRRK2-G2019S variant restricts serine metabolism, leading to microglial inflammation and dopaminergic neuron degeneration.Journal of neuroinflammation · 2025Article
- Lrrk2 G2019S mutation incites increased cell-intrinsic neutrophil effector functions and intestinal inflammation in a model of infectious colitis.NPJ Parkinson's disease · 2025Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease-associated kinase LRRK2 has been linked to IFN type II (IFN-γ) response in infections and to dopaminergic neuronal loss. However, whether and how LRRK2 synergizes with IFN-γ remains unclear. In this study, we employed dopaminergic neurons and microglia differentiated from patient-derived induced pluripotent stem cells carrying LRRK2 G2019S, the most common Parkinson's disease-associated mutation. We show that IFN-γ enhances the LRRK2 G2019S-dependent negative regulation of AKT phosphorylation and NFAT activation, thereby increasing neuronal vulnerability to immune challenge. Mechanistically, LRRK2 G2019S suppresses NFAT translocation via calcium signaling and possibly through microtubule reorganization. In microglia, LRRK2 modulates cytokine production and the glycolytic switch in response to IFN-γ in an NFAT-independent manner. Activated LRRK2 G2019S microglia cause neurite shortening, indicating that LRRK2-driven immunological changes can be neurotoxic. We propose that synergistic LRRK2/IFN-γ activation serves as a potential link between inflammation and neurodegeneration in Parkinson's disease.
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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.