ArticleNeurobiology of disease2010
Impaired dopaminergic neurotransmission and microtubule-associated protein tau alterations in human LRRK2 transgenic mice.
Article in Neurobiology of disease, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers.
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Who cites it
155 citing papers in PubMed, 277 citations in OpenAlex.
- Rodent models and accompanying in vitro strategies for studying the etiology and therapy of Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Neuroinflammatory and Motor Alterations in LRRK2*G2019S Transgenic Mice Without Enhanced Vulnerability to Aging or Chronic MPTP-Induced Nigrostriatal Neurodegeneration.Journal of neurochemistry · 2026Article
- Strategies for Optimizing Genetic Mouse Models to Enhance the Understanding of Parkinson's Disease.Biomedicines · 2026Review
- Targeting of kinases to treat neurodegenerative diseases.Pharmacological reviews · 2026Review
- Synergistic Effects of Multi-Kinase Inhibition onBiomedicines · 2026Article
- LRRK2 kinase-mediated accumulation of lysosome-associated phospho-Rabs in tauopathies and synucleinopathies.Acta neuropathologica · 2025Article
- LRRK2 kinase modulates glucose-stimulated insulin secretion via RAB8 phosphorylation and ciliogenesis.Cellular and molecular life sciences : CMLS · 2025Article
- The homozygous LRRK2.p.N1437D point mutation mouse is a novel model of parkinsonism.NPJ Parkinson's disease · 2025Article
- Loss of LRRK2 activity induces cytoskeleton defects and oxidative stress during porcine oocyte maturation.Cell communication and signaling : CCS · 2025Article
- Roles of LRRK2 and its orthologs in protecting against neurodegeneration and neurodevelopmental defects.Frontiers in cell and developmental biology · 2025Article
- Parkinson's disease gene, Synaptojanin1, dysregulates the surface maintenance of the dopamine transporter.NPJ Parkinson's disease · 2024Article
- Cell-autonomous role of leucine-rich repeat kinase in the protection of dopaminergic neuron survival.eLife · 2024Article
- Review
- Sex-dependent interactions between prodromal intestinal inflammation and LRRK2 G2019S in mice promote endophenotypes of Parkinson's disease.Communications biology · 2024Article
- The LRRK2 kinase substrates RAB8a and RAB10 contribute complementary but distinct disease-relevant phenotypes in human neurons.Stem cell reports · 2024Article
- Cellular and subcellular localization of Rab10 and phospho-T73 Rab10 in the mouse and human brain.Acta neuropathologica communications · 2023Article
- Modeling Parkinson's disease in LRRK2 rodents.Neuronal signaling · 2023Review
- Impaired dopamine release in Parkinson's disease.Brain : a journal of neurology · 2023Review
- Animal models of Parkinson's disease: bridging the gap between disease hallmarks and research questions.Translational neurodegeneration · 2023Review
- Age- and Sex-Dependent Behavioral and Neurochemical Alterations in hLRRK2-G2019S BAC Mice.Biomolecules · 2022Article
95 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 5 institutions in 2 countries.
Funding
Abstract
Mutations in the Leucine Rich Repeat Kinase 2 (LRRK2) gene, first described in 2004 have now emerged as the most important genetic finding in both autosomal dominant and sporadic Parkinson's disease (PD). While a formidable research effort has ensued since the initial gene discovery, little is known of either the normal or the pathological role of LRRK2. We have created lines of mice that express human wild-type (hWT) or G2019S Lrrk2 via bacterial artificial chromosome (BAC) transgenesis. In vivo analysis of the dopaminergic system revealed abnormal dopamine neurotransmission in both hWT and G2019S transgenic mice evidenced by a decrease in extra-cellular dopamine levels, which was detected without pharmacological manipulation. Immunopathological analysis revealed changes in localization and increased phosphorylation of microtubule binding protein tau in G2019S mice. Quantitative biochemical analysis confirmed the presence of differential phospho-tau species in G2019S mice but surprisingly, upon dephosphorylation the tau isoform banding pattern in G2019S mice remained altered. This suggests that other post-translational modifications of tau occur in G2019S mice. We hypothesize that Lrrk2 may impact on tau processing which subsequently leads to increased phosphorylation. Our models will be useful for further understanding of the mechanistic actions of LRRK2 and future therapeutic screening.
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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.