ArticleNeurobiology of disease2015
Progressive dopaminergic alterations and mitochondrial abnormalities in LRRK2 G2019S knock-in mice.
Article in Neurobiology of disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 167 papers.
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Who cites it
167 citing papers in PubMed, 274 citations in OpenAlex.
- Protocol to quantify LRRK2-mediated Rab10 phosphorylation using high-content imaging.STAR protocols · 2026Article
- Chronic Methamphetamine Administration Increases Mitochondrial Density and Impairs Mitochondrial Function in the Substantia Nigra Pars Compacta.Journal of neurochemistry · 2026Article
- Neuroinflammatory and Motor Alterations in LRRK2*G2019S Transgenic Mice Without Enhanced Vulnerability to Aging or Chronic MPTP-Induced Nigrostriatal Neurodegeneration.Journal of neurochemistry · 2026Article
- Rodent models and accompanying in vitro strategies for studying the etiology and therapy of Parkinson's disease.Journal of Parkinson's disease · 2026Review
- Nigrostriatal dopaminergic vulnerability in Parkinson's disease: Neuroprotective strategies.Neural regeneration research · 2026Article
- Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons.Nature communications · 2026Article
- Parkinson's disease LRRK2 mutations dysregulate iron homeostasis and promote oxidative stress and ferroptosis in human neurons and astrocytes.Molecular neurodegeneration · 2026Article
- Diffusion Magnetic Resonance Imaging of Cortical Microstructure Differs in Nonmanifest and Manifest Genetic Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- LRRK2 I1371V Mutation Drives Astrocytic Glucose Metabolism Failure and Induces Integrated ER-Mitochondria-Lysosome Dysfunction in Parkinson's Disease.International journal of molecular sciences · 2026Article
- Role of LRRK2 in physiological activities, diseases, and therapy.Chinese medical journal · 2026Review
- Parkinson's disease linked LRRK2 G2019S drives oxidative nuclear DNA damage and PARP1 hyperactive signaling.bioRxiv : the preprint server for biology · 2026Article
- Extracellular Vesicle-Mediated Delivery of Constrained Peptides Disrupts the Pathogenic Interaction of LRRK2-FADD in Parkinson's Disease.Journal of extracellular biology · 2026Article
- Inflammatory signaling differentially changes chromatin accessibility and gene expression of the PD- associated kinase LRRK2 between human and mice.bioRxiv : the preprint server for biology · 2026Article
- Cell-Free DNA and Mitochondria in Parkinson's Disease.International journal of molecular sciences · 2025Review
- Alpha-Synuclein Neurobiology in Parkinson's Disease: A Comprehensive Review of Its Role, Mechanisms, and Therapeutic Perspectives.Brain sciences · 2025Review
- LRRK2 mediates haloperidol-induced changes in indirect pathway striatal projection neurons.Molecular psychiatry · 2025Article
- Regulation of LRRK2 activity by metabolic stress and heavy metal exposure.Brain research · 2025Article
- Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons.bioRxiv : the preprint server for biology · 2025Article
- Lrrk2 G2019S mutation incites increased cell-intrinsic neutrophil effector functions and intestinal inflammation in a model of infectious colitis.NPJ Parkinson's disease · 2025Article
- Recent advances in targeting LRRK2 for Parkinson's disease treatment.Journal of translational medicine · 2025Review
107 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
Abstract
Mutations in the LRRK2 gene represent the most common genetic cause of late onset Parkinson's disease. The physiological and pathological roles of LRRK2 are yet to be fully determined but evidence points towards LRRK2 mutations causing a gain in kinase function, impacting on neuronal maintenance, vesicular dynamics and neurotransmitter release. To explore the role of physiological levels of mutant LRRK2, we created knock-in (KI) mice harboring the most common LRRK2 mutation G2019S in their own genome. We have performed comprehensive dopaminergic, behavioral and neuropathological analyses in this model up to 24months of age. We find elevated kinase activity in the brain of both heterozygous and homozygous mice. Although normal at 6months, by 12months of age, basal and pharmacologically induced extracellular release of dopamine is impaired in both heterozygous and homozygous mice, corroborating previous findings in transgenic models over-expressing mutant LRRK2. Via in vivo microdialysis measurement of basal and drug-evoked extracellular release of dopamine and its metabolites, our findings indicate that exocytotic release from the vesicular pool is impaired. Furthermore, profound mitochondrial abnormalities are evident in the striatum of older homozygous G2019S KI mice, which are consistent with mitochondrial fission arrest. We anticipate that this G2019S mouse line will be a useful pre-clinical model for further evaluation of early mechanistic events in LRRK2 pathogenesis and for second-hit approaches to model disease progression.
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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.