ArticlePLoS biology2018
Lrrk promotes tau neurotoxicity through dysregulation of actin and mitochondrial dynamics.
Article in PLoS biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 2 of them syntheses that pooled it.
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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
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Who cites it
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 55 citations in OpenAlex.
- MAM kinases: physiological roles, related diseases, and therapeutic perspectives-a systematic review.Cellular & molecular biology letters · 2025Pooled it
- Molecular Pathways Involved in LRRK2-Linked Parkinson's Disease: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Rodent models and accompanying in vitro strategies for studying the etiology and therapy of Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Mitochondria and the Actin Cytoskeleton in Neurodegeneration.Cytoskeleton (Hoboken, N.J.) · 2026Review
- Exploring the versatility ofFly · 2025Review
- Mitophagy in perioperative neurocognitive disorder: mechanisms and therapeutic strategies.European journal of medical research · 2025Review
- Analysis of C9orf72 repeat length in progressive supranuclear palsy, corticobasal syndrome, corticobasal degeneration, and atypical parkinsonism.Journal of neurology · 2025Article
- Accumulation of F-actin drives brain aging and limits healthspan in Drosophila.Nature communications · 2024Article
- LRRK2 Kinase Inhibitor PF-06447475 Protects Drosophila melanogaster against Paraquat-Induced Locomotor Impairment, Life Span Reduction, and Oxidative Stress.Neurochemical research · 2024Article
- Transcriptional programs mediating neuronal toxicity and altered glial-neuronal signaling in aGenome research · 2024Article
- Transcriptional programs mediating neuronal toxicity and altered glial-neuronal signaling in abioRxiv : the preprint server for biology · 2024Article
- The causal effects of intelligence and fluid intelligence on Parkinson's disease: a Mendelian randomization study.Frontiers in aging neuroscience · 2024Article
- Prospective Role of PAK6 and 14-3-3γ as Biomarkers for Parkinson's Disease.Journal of Parkinson's disease · 2024Article
- Simple model systems reveal conserved mechanisms of Alzheimer's disease and related tauopathies.Molecular neurodegeneration · 2023Review
- Multifaceted functions of Drp1 in hypoxia/ischemia-induced mitochondrial quality imbalance: from regulatory mechanism to targeted therapeutic strategy.Military Medical Research · 2023Review
- Animal models of Parkinson's disease: bridging the gap between disease hallmarks and research questions.Translational neurodegeneration · 2023Review
- Insights fromFrontiers in neuroscience · 2023Review
- Actin-binding protein filamin-A drives tau aggregation and contributes to progressive supranuclear palsy pathology.Science advances · 2022Article
- Roles of α-Synuclein and Disease-Associated Factors inInternational journal of molecular sciences · 2022Review
- Neuronal cell death mechanisms in Alzheimer's disease: An insight.Frontiers in molecular neuroscience · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson disease. Genetics and neuropathology link Parkinson disease with the microtubule-binding protein tau, but the mechanism of action of LRRK2 mutations and the molecular connection between tau and Parkinson disease are unclear. Here, we investigate the interaction of LRRK and tau in Drosophila and mouse models of tauopathy. We find that either increasing or decreasing the level of fly Lrrk enhances tau neurotoxicity, which is further exacerbated by expressing Lrrk with dominantly acting Parkinson disease-associated mutations. At the cellular level, altering Lrrk expression promotes tau neurotoxicity via excess stabilization of filamentous actin (F-actin) and subsequent mislocalization of the critical mitochondrial fission protein dynamin-1-like protein (Drp1). Biochemically, monomeric LRRK2 exhibits actin-severing activity, which is reduced as increasing concentrations of wild-type LRRK2, or expression of mutant forms of LRRK2 promote oligomerization of the protein. Overall, our findings provide a potential mechanistic basis for a dominant negative mechanism in LRRK2-mediated Parkinson disease, suggest a common molecular pathway with other familial forms of Parkinson disease linked to abnormalities of mitochondrial dynamics and quality control, and raise the possibility of new therapeutic approaches to Parkinson disease and related disorders.
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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.