ArticlePLoS genetics2015
The Parkinson's Disease-Associated Protein Kinase LRRK2 Modulates Notch Signaling through the Endosomal Pathway.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 71 citations in OpenAlex.
- An LRRK2 variant blocks NCOA4 trafficking upon iron overload, leading to ferroptotic death.Journal of cell science · 2026Article
- DNAJC6 Parkinson's disease: Endolysosomal dysfunction and emerging roles for oligodendrocytes.NPJ Parkinson's disease · 2026Review
- What role does the Notch signaling pathway play in exercise-related metabolic and neurological adaptations? A molecular-to-systems perspective.Frontiers in physiology · 2026Review
- E3 ubiquitin ligases in neurodegenerative diseases.Military Medical Research · 2026Review
- A Spatially Resolved View on the Aging Substantia nigra: An Exploratory Proteomic Study.Advanced biology · 2025Article
- Endosomal traffic disorders: a driving force behind neurodegenerative diseases.Translational neurodegeneration · 2024Review
- Hepatocyte-Targeted Lipid Nanoparticle Delivery of HERC2 Plasmid Controls Drug-Induced Hepatotoxicity by Limiting β-Catenin-Regulated CYP2E1 Expression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The disordered negatively charged C-terminus of the large HECT E3 ubiquitin ligase HERC2 provides structural and thermal stability to the HECT C-lobe.Protein science : a publication of the Protein Society · 2024Article
- Unraveling Dysregulated Cell Signaling Pathways, Genetic and Epigenetic Mysteries of Parkinson's Disease.Molecular neurobiology · 2024Review
- Single-cell transcriptomic and proteomic analysis of Parkinson's disease brains.Science translational medicine · 2024Article
- Early-stage idiopathic Parkinson's disease is associated with reduced circular RNA expression.NPJ Parkinson's disease · 2024Article
- Primary cilia in Parkinson's disease: summative roles in signaling pathways, genes, defective mitochondrial function, and substantia nigra dopaminergic neurons.Frontiers in aging neuroscience · 2024Review
- Article
- Coordinated modification in expression levels of HSPA1A/B, DGKH, and NOTCH2 in Parkinson's patients' blood and substantia nigra as a diagnostic sign: the transcriptomes' relationship.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Article
- Therapeutic potential of melatonin and its derivatives in aging and neurodegenerative diseases.Biogerontology · 2023Review
- Effect of CPP-related genes on GnRH secretion and Notch signaling pathway during puberty.Biomedical journal · 2023Review
- Regulation of MAPK Signaling Pathways by the Large HERC Ubiquitin Ligases.International journal of molecular sciences · 2023Review
- Differential serum microRNAs in premotor LRRK2 G2019S carriers from Parkinson's disease.NPJ Parkinson's disease · 2023Article
- HERC2 promotes inflammation-driven cancer stemness and immune evasion in hepatocellular carcinoma by activating STAT3 pathway.Journal of experimental & clinical cancer research : CR · 2023Article
- From 2D to 3D: Development of Monolayer Dopaminergic Neuronal and Midbrain Organoid Cultures for Parkinson's Disease Modeling and Regenerative Therapy.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leucine-rich repeat kinase 2 (LRRK2) is a key molecule in the pathogenesis of familial and idiopathic Parkinson's disease (PD). We have identified two novel LRRK2-associated proteins, a HECT-type ubiquitin ligase, HERC2, and an adaptor-like protein with six repeated Neuralized domains, NEURL4. LRRK2 binds to NEURL4 and HERC2 via the LRRK2 Ras of complex proteins (ROC) domain and NEURL4, respectively. HERC2 and NEURL4 link LRRK2 to the cellular vesicle transport pathway and Notch signaling, through which the LRRK2 complex promotes the recycling of the Notch ligand Delta-like 1 (Dll1)/Delta (Dl) through the modulation of endosomal trafficking. This process negatively regulates Notch signaling through cis-inhibition by stabilizing Dll1/Dl, which accelerates neural stem cell differentiation and modulates the function and survival of differentiated dopaminergic neurons. These effects are strengthened by the R1441G ROC domain-mutant of LRRK2. These findings suggest that the alteration of Notch signaling in mature neurons is a component of PD etiology linked to LRRK2.
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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.