ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
A rat model of progressive nigral neurodegeneration induced by the Parkinson's disease-associated G2019S mutation in LRRK2.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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78 citing papers in PubMed, 147 citations in OpenAlex.
- LRRK2 as a Potential Disease-Modifying Target in Sporadic Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Review
- Role of Microglial Dysfunction in Parkinson's Disease: From Multifactorial Causes to Neurodegeneration.Neuroscience bulletin · 2026Review
- Experimental Models and Translational Strategies in Neuroprotective Drug Development with Emphasis on Alzheimer's Disease.Molecules (Basel, Switzerland) · 2026Review
- The G2019S LRRK2 mutation exacerbates α-synuclein and tau neuropathology through divergent pathways in Parkinson's disease models.Acta neuropathologica · 2025Article
- Modeling of Parkinson's Disease in Different Models.CNS & neurological disorders drug targets · 2025Review
- The design and development of LRRK2 inhibitors as novel therapeutics for Parkinson's disease.Future medicinal chemistry · 2025Review
- Roles of LRRK2 and its orthologs in protecting against neurodegeneration and neurodevelopmental defects.Frontiers in cell and developmental biology · 2025Article
- Aging, Parkinson's Disease, and Models: What Are the Challenges?Aging biology · 2023Article
- Emerging targets signaling for inflammation in Parkinson's disease drug discovery.Metabolic brain disease · 2022Review
- Exploring the focal role of LRRK2 kinase in Parkinson's disease.Environmental science and pollution research international · 2022Review
- Evaluation of Current Methods to Detect Cellular Leucine-Rich Repeat Kinase 2 (LRRK2) Kinase Activity.Journal of Parkinson's disease · 2022Article
- Deletion of lrrk2 causes early developmental abnormalities and age-dependent increase of monoamine catabolism in the zebrafish brain.PLoS genetics · 2021Article
- Adeno-Associated Viral Vectors as Versatile Tools for Parkinson's Research, Both for Disease Modeling Purposes and for Therapeutic Uses.International journal of molecular sciences · 2021Review
- Development of a physiologically relevant and easily scalable LUHMES cell-based model of G2019S LRRK2-driven Parkinson's disease.Disease models & mechanisms · 2021Article
- An Emerging Role for Phosphoinositides in the Pathophysiology of Parkinson's Disease.Journal of Parkinson's disease · 2021Review
- Machine learning discriminates a movement disorder in a zebrafish model of Parkinson's disease.Disease models & mechanisms · 2020Article
- Dopaminergic neurodegeneration induced by Parkinson's disease-linked G2019S LRRK2 is dependent on kinase and GTPase activity.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- CAV-2-Mediated GFP and LRRK2Frontiers in molecular neuroscience · 2020Article
- Clinically Precedented Protein Kinases: Rationale for Their Use in Neurodegenerative Disease.Frontiers in aging neuroscience · 2020Review
- LRRK2 and Protein Aggregation in Parkinson's Disease: Insights From Animal Models.Frontiers in neuroscience · 2020Review
18 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The G2019S mutation in the leucine-rich repeat kinase 2 (LRRK2) gene is the most common genetic cause of Parkinson's disease (PD), accounting for a significant proportion of both autosomal dominant familial and sporadic PD cases. Our aim in the present study is to generate a mammalian model of mutant G2019S LRRK2 pathogenesis, which reproduces the robust nigral neurodegeneration characteristic of PD. We developed adenoviral vectors to drive neuron-specific expression of full-length wild-type or mutant G2019S human LRRK2 in the nigrostriatal system of adult rats. Wild-type LRRK2 did not induce any significant neuronal loss. In contrast, under the same conditions and levels of expression, G2019S mutant LRRK2 causes a progressive degeneration of nigral dopaminergic neurons. Our data provide a novel rat model of PD, based on a prevalent genetic cause, that reproduces a cardinal feature of the disease within a rapid time frame suitable for testing of neuroprotective strategies.
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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.