ArticleJournal of neurochemistry2014
Interferon-γ induces leucine-rich repeat kinase LRRK2 via extracellular signal-regulated kinase ERK5 in macrophages.
Article in Journal of neurochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 71 citations in OpenAlex.
- Colonic LRRK2 expression is increased in Crohn's disease but not in Parkinson's disease and idiopathic RBD.Acta neuropathologica · 2026Article
- Subtype-specific secretion of extracellular vesicles by LRRK2 and Rab GTPases under lysosomal stress.iScience · 2026Article
- Recent advances in targeting LRRK2 for Parkinson's disease treatment.Journal of translational medicine · 2025Review
- Inflammation and IL-4 regulate Parkinson's and Crohn's disease associated kinase LRRK2.EMBO reports · 2025Article
- Differentiation and regulation of CD4Cellular and molecular life sciences : CMLS · 2024Review
- Article
- Blocking IL-6 signaling prevents astrocyte-induced neurodegeneration in an iPSC-based model of Parkinson's disease.JCI insight · 2024Article
- LRRK2; Communicative Role in the Treatment of Parkinson's Disease and Ulcerative Colitis Overlapping.CNS & neurological disorders drug targets · 2024Review
- Targeting leucine-rich repeat serine/threonine-protein kinase 2 sensitizes pancreatic ductal adenocarcinoma to anti-PD-L1 immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- The contribution of inflammatory astrocytes to BBB impairments in a brain-chip model of Parkinson's disease.Nature communications · 2023Article
- The interplay between monocytes, α-synuclein and LRRK2 in Parkinson's disease.Biochemical Society transactions · 2023Review
- Characterization of Lipopolysaccharide Effects on LRRK2 Signaling in RAW Macrophages.International journal of molecular sciences · 2023Article
- Inflammation and immune dysfunction in Parkinson disease.Nature reviews. Immunology · 2022Review
- Immune Response Modifications in the Genetic Forms of Parkinson's Disease: What Do We Know?International journal of molecular sciences · 2022Review
- Mutant LRRK2 in lymphocytes regulates neurodegeneration via IL-6 in an inflammatory model of Parkinson's disease.NPJ Parkinson's disease · 2022Article
- G2019SFrontiers in neuroscience · 2022Article
- WHOPPA Enables Parallel Assessment of Leucine-Rich Repeat Kinase 2 and Glucocerebrosidase Enzymatic Activity in Parkinson's Disease Monocytes.Frontiers in cellular neuroscience · 2022Article
- The Double-Faceted Role of Leucine-Rich Repeat Kinase 2 in the Immunopathogenesis of Parkinson's Disease.Frontiers in aging neuroscience · 2022Review
- Unraveling Parkinson's Disease Neurodegeneration: Does Aging Hold the Clues?Journal of Parkinson's disease · 2022Review
- Abrogation of LRRK2 dependent Rab10 phosphorylation with TLR4 activation and alterations in evoked cytokine release in immune cells.Neurochemistry international · 2021Article
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The gene encoding leucine-rich repeat kinase 2 (LRRK2) comprises a major risk factor for Parkinson's disease. Recently, it has emerged that LRRK2 plays important roles in the immune system. LRRK2 is induced by interferon-γ (IFN-γ) in monocytes, but the signaling pathway is not known. Here, we show that IFN-γ-mediated induction of LRRK2 was suppressed by pharmacological inhibition and RNA interference of the extracellular signal-regulated kinase 5 (ERK5). This was confirmed by LRRK2 immunostaining, which also revealed that the morphological responses to IFN-γ were suppressed by ERK5 inhibitor treatment. Both human acute monocytic leukemia THP-1 cells and human peripheral blood monocytes stimulated the ERK5-LRRK2 pathway after differentiation into macrophages. Thus, LRRK2 is induced via a novel, ERK5-dependent IFN-γ signal transduction pathway, pointing to new functions of ERK5 and LRRK2 in human macrophages. Leucine-rich repeat kinase 2 (LRRK2) is a major risk factor for the development of Parkinson's disease (PD). However, the role of LRRK2 in the affected neurons remains enigmatic. Recently, LRRK2 has been reported to be strongly expressed in the immune system. Here, we demonstrate that LRRK2 is induced by Interferon gamma via extracellular signal-regulated kinase 5 (ERK5) in macrophages, thus providing new insights in LRRK2 and ERK5 biology.
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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.