ArticleNature communications2018
LRRK2 kinase regulates α-synuclein propagation via RAB35 phosphorylation.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 93 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.
- Molecular Pathways Involved in LRRK2-Linked Parkinson's Disease: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Knockout of the LRRK2-counteracting RAB phosphatase PPM1H disrupts axonal autophagy and exacerbates alpha-synuclein aggregation.Cell reports · 2026Article
- MicroRNA-181 influences Alzheimer's risk by regulating neprilysin and microtubule-associated tau pathways, offering a novel target.bioRxiv : the preprint server for biology · 2026Article
- The Dual Role of Glial Extracellular Vesicles in Neurodegeneration: Insights from iPSC-Based Models.International journal of molecular sciences · 2026Review
- Review
- Article
- Article
- LRRK2 as a Potential Disease-Modifying Target in Sporadic Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Review
- Nucleic acid therapeutics in neurodegenerative disorders: emerging technologies and clinical landscape.Molecular neurodegeneration advances · 2026Review
- Linking primary cilia defects to the "Big 3" neurodegenerative diseases - causal, consequential, or correlative?EXCLI journal · 2026Article
- LRRK2 and the fragile synapse: a molecular prelude to Parkinson's disease?The Biochemical journal · 2025Review
- Genetic mutations in kinases: a comprehensive review on marketed inhibitors and unexplored targets in Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Unraveling Molecular Targets for Neurodegenerative Diseases ThroughInternational journal of molecular sciences · 2025Review
- Chaperones as Potential Pharmacological Targets for Treating Protein Aggregation Illness.Current protein & peptide science · 2025Review
- Endosomal traffic disorders: a driving force behind neurodegenerative diseases.Translational neurodegeneration · 2024Review
- Impairment of the Glial Phagolysosomal System Drives Prion-Like Propagation in aThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Expression of G2019S LRRK2 in Rat Primary Astrocytes Mediates Neurotoxicity and Alters the Dopamine Synthesis Pathway in N27 Cells via Astrocytic Proinflammatory Cytokines and Neurotrophic Factors.Current issues in molecular biology · 2024Article
- Exploring Caenorhabditis elegans as Parkinson's Disease Model: Neurotoxins and Genetic Implications.Neurotoxicity research · 2024Review
- Impairment of the glial phagolysosomal system drives prion-like propagation in abioRxiv : the preprint server for biology · 2024Article
- Review
33 more citing papers are in PubMed but not listed here.
Corrections and comments
- Retracted
Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
Abstract
Propagation of α-synuclein aggregates has been suggested as a contributing factor in Parkinson's disease (PD) progression. However, the molecular mechanisms underlying α-synuclein aggregation are not fully understood. Here, we demonstrate in cell culture, nematode, and rodent models of PD that leucine-rich repeat kinase 2 (LRRK2), a PD-linked kinase, modulates α-synuclein propagation in a kinase activity-dependent manner. The PD-linked G2019S mutation in LRRK2, which increases kinase activity, enhances propagation efficiency. Furthermore, we show that the role of LRRK2 in α-synuclein propagation is mediated by RAB35 phosphorylation. Constitutive activation of RAB35 overrides the reduced α-synuclein propagation phenotype in lrk-1 mutant C. elegans. Finally, in a mouse model of synucleinopathy, administration of an LRRK2 kinase inhibitor reduced α-synuclein aggregation via enhanced interaction of α-synuclein with the lysosomal degradation pathway. These results suggest that LRRK2-mediated RAB35 phosphorylation is a potential therapeutic target for modifying disease progression.
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What OpenQuestion holds
Registered trials
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.