ArticlePloS one2012
High LRRK2 levels fail to induce or exacerbate neuronal alpha-synucleinopathy in mouse brain.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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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.
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Who cites it
49 citing papers in PubMed, 74 citations in OpenAlex.
- Strategies for Optimizing Genetic Mouse Models to Enhance the Understanding of Parkinson's Disease.Biomedicines · 2026Review
- α-Synuclein in Lewy Body Diseases: Progress, Remaining Challenges and Future Perspectives.Expert reviews in molecular medicine · 2026Review
- Widespread distribution of α-synuclein oligomers in LRRK2-related Parkinson's disease.Acta neuropathologica · 2025Article
- Viral mediated α-synuclein overexpression results in greater transgene levels and α-synuclein overload in mice bearing kinase dead mutation of LRRK2.Scientific reports · 2025Article
- Affective phenotypes in heterozygousFrontiers in genetics · 2025Article
- Formation of templated inclusions in a forebrain α-synuclein mouse model is independent of LRRK2.Neurobiology of disease · 2023Article
- Modeling Parkinson's disease in LRRK2 rodents.Neuronal signaling · 2023Review
- Perspective on the current state of the LRRK2 field.NPJ Parkinson's disease · 2023Review
- Salivary levels of disease-related biomarkers in the early stages of Parkinson's and Alzheimer's disease:IBRO neuroscience reports · 2023Article
- Translating Pathological Brain Activity Primers in Parkinson's Disease Research.Research (Washington, D.C.) · 2023Review
- Human Induced Pluripotent Stem Cell Phenotyping and Preclinical Modeling of Familial Parkinson's Disease.Genes · 2022Review
- LRRK2 and Proteostasis in Parkinson's Disease.International journal of molecular sciences · 2022Review
- LRRK2 along the Golgi and lysosome connection: a jamming situation.Biochemical Society transactions · 2021Review
- Comprehensive Perspectives on Experimental Models for Parkinson's Disease.Aging and disease · 2021Review
- LRRK2 Kinase Activity Does Not Alter Cell-Autonomous Tau Pathology Development in Primary Neurons.Journal of Parkinson's disease · 2021Article
- Pathogenic LRRK2 requires secondary factors to induce cellular toxicity.Bioscience reports · 2020Article
- LRRK2 and α-Synuclein: Distinct or Synergistic Players in Parkinson's Disease?Frontiers in neuroscience · 2020Review
- From Synaptic Dysfunction to Neuroprotective Strategies in Genetic Parkinson's Disease: Lessons From LRRK2.Frontiers in cellular neuroscience · 2020Review
- Progress inFrontiers in neuroscience · 2020Review
- LRRK2 and Protein Aggregation in Parkinson's Disease: Insights From Animal Models.Frontiers in neuroscience · 2020Review
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The G2019S mutation in the multidomain protein leucine-rich repeat kinase 2 (LRRK2) is one of the most frequently identified genetic causes of Parkinson's disease (PD). Clinically, LRRK2(G2019S) carriers with PD and idiopathic PD patients have a very similar disease with brainstem and cortical Lewy pathology (α-synucleinopathy) as histopathological hallmarks. Some patients have Tau pathology. Enhanced kinase function of the LRRK2(G2019S) mutant protein is a prime suspect mechanism for carriers to develop PD but observations in LRRK2 knock-out, G2019S knock-in and kinase-dead mutant mice suggest that LRRK2 steady-state abundance of the protein also plays a determining role. One critical question concerning the molecular pathogenesis in LRRK2(G2019S) PD patients is whether α-synuclein (aSN) has a contributory role. To this end we generated mice with high expression of either wildtype or G2019S mutant LRRK2 in brainstem and cortical neurons. High levels of these LRRK2 variants left endogenous aSN and Tau levels unaltered and did not exacerbate or otherwise modify α-synucleinopathy in mice that co-expressed high levels of LRRK2 and aSN in brain neurons. On the contrary, in some lines high LRRK2 levels improved motor skills in the presence and absence of aSN-transgene-induced disease. Therefore, in many neurons high LRRK2 levels are well tolerated and not sufficient to drive or exacerbate neuronal α-synucleinopathy.
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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.