ArticleProceedings of the National Academy of Sciences of the United States of America2018
Robust kinase- and age-dependent dopaminergic and norepinephrine neurodegeneration in LRRK2 G2019S transgenic mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Molecular Pathways Involved in LRRK2-Linked Parkinson's Disease: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons.Nature communications · 2026Article
- In vivo Proximity & Spatial Proteomics with CRISPR Screening Identify STXBP1 as a Protective Modifier of α-synuclein Toxicity in Dopamine Neurons.bioRxiv : the preprint server for biology · 2026Article
- Experimental Models and Translational Strategies in Neuroprotective Drug Development with Emphasis on Alzheimer's Disease.Molecules (Basel, Switzerland) · 2026Review
- Molecular Mechanisms of Dopaminergic Neuron Degeneration in Parkinson's Disease: A Comprehensive Review.Current neuropharmacology · 2026Review
- Leucine-rich repeat kinase 2 impairs the release sites of Parkinson's disease vulnerable dopamine axons.bioRxiv : the preprint server for biology · 2025Article
- Dopamine D2 receptor upregulation in dorsal striatum in the LRRK2-R1441C rat model of early Parkinson's disease revealed by in vivo PET imaging.Scientific reports · 2025Article
- Environmental Factors Exacerbate Parkinsonian Phenotypes in an Asian-Specific Knock-In LRRK2 Risk Variant in Mice.International journal of molecular sciences · 2025Article
- An update on mammalian and non-mammalian animal models for biomarker development in neurodegenerative disorders.Cellular and molecular life sciences : CMLS · 2025Review
- Short-term lipopolysaccharide treatment leads to astrocyte activation in LRRK2 G2019S knock-in mice without loss of dopaminergic neurons.BMC neuroscience · 2025Article
- Drug discovery and development for Parkinson's disease: are preclinical models good enough?Frontiers in aging neuroscience · 2025Review
- Exploring LRRK2-dependent Mechanisms in Parkinson's Disease Therapy.CNS & neurological disorders drug targets · 2025Review
- CalDAG-GEFI acts as a guanine nucleotide exchange factor for LRRK2 to regulate LRRK2 function and neurodegeneration.Science advances · 2024Article
- Natural variation in age-related dopamine neuron degeneration is glutathione dependent and linked to life span.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Cell-autonomous role of leucine-rich repeat kinase in the protection of dopaminergic neuron survival.eLife · 2024Article
- Neurodevelopmental and synaptic defects in DNAJC6 parkinsonism, amenable to gene therapy.Brain : a journal of neurology · 2024Article
- Disruption of Dopamine Homeostasis Associated with Alteration of Proteins in Synaptic Vesicles: A Putative Central Mechanism of Parkinson's Disease Pathogenesis.Aging and disease · 2024Review
- Short-term lipopolysaccharide treatment leads to astrocyte activation in LRRK2 G2019S knock-in mice without loss of dopaminergic neurons.Research square · 2024Article
- How Parkinson's Disease-Linked LRRK2 Mutations Affect Different CNS Cell Types.Journal of Parkinson's disease · 2024Review
- Modeling Parkinson's disease in LRRK2 rodents.Neuronal signaling · 2023Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 1 country.
Funding
Abstract
Mutations in LRRK2 are known to be the most common genetic cause of sporadic and familial Parkinson's disease (PD). Multiple lines of LRRK2 transgenic or knockin mice have been developed, yet none exhibit substantial dopamine (DA)-neuron degeneration. Here we develop human tyrosine hydroxylase (TH) promoter-controlled tetracycline-sensitive LRRK2 G2019S (GS) and LRRK2 G2019S kinase-dead (GS/DA) transgenic mice and show that LRRK2 GS expression leads to an age- and kinase-dependent cell-autonomous neurodegeneration of DA and norepinephrine (NE) neurons. Accompanying the loss of DA neurons are DA-dependent behavioral deficits and α-synuclein pathology that are also LRRK2 GS kinase-dependent. Transmission EM reveals that that there is an LRRK2 GS kinase-dependent significant reduction in synaptic vesicle number and a greater abundance of clathrin-coated vesicles in DA neurons. These transgenic mice indicate that LRRK2-induced DA and NE neurodegeneration is kinase-dependent and can occur in a cell-autonomous manner. Moreover, these mice provide a substantial advance in animal model development for LRRK2-associated PD and an important platform to investigate molecular mechanisms for how DA neurons degenerate as a result of expression of mutant LRRK2.
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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.