ArticleCNS neuroscience & therapeutics2017
Effects of LRRK2 Inhibitors on Nigrostriatal Dopaminergic Neurotransmission.
Article in CNS neuroscience & therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- The human LRRK2-R1441G mutation drives age-dependent oxidative stress and mitochondrial dysfunction in dopaminergic neurons.Molecular neurodegeneration · 2026Article
- Disruption of the LRRK2 substrate RAB12 facilitates neurotransmission and causes hyperactivity in mice.NPJ Parkinson's disease · 2026Article
- Role of LRRK2 in physiological activities, diseases, and therapy.Chinese medical journal · 2026Review
- Modeling Parkinson's disease in LRRK2 rodents.Neuronal signaling · 2023Review
- Aberrant somatic calcium channel function in cNurr1 and LRRK2-G2019S mice.NPJ Parkinson's disease · 2023Article
- Neuronal Firing and Glutamatergic Synapses in the Substantia Nigra Pars Reticulata of LRRK2-G2019S Mice.Biomolecules · 2022Article
- The Role of Rab Proteins in Parkinson's Disease Synaptopathy.Biomedicines · 2022Review
- Exploring the focal role of LRRK2 kinase in Parkinson's disease.Environmental science and pollution research international · 2022Review
- LRRK2-G2019S mice display alterations in glutamatergic synaptic transmission in midbrain dopamine neurons.Journal of neurochemistry · 2022Article
- Targeting autophagy using small-molecule compounds to improve potential therapy of Parkinson's disease.Acta pharmaceutica Sinica. B · 2021Review
- Progressive parkinsonism due to mitochondrial impairment: Lessons from the MitoPark mouse model.Experimental neurology · 2021Review
- Review-Recent Advances in FSCV Detection of Neurochemicals via Waveform and Carbon Microelectrode Modification.Journal of the Electrochemical Society · 2021Article
- Article
- Review
- Leucine-rich repeat kinase 2 (LRRK2) inhibitors differentially modulate glutamate release and Serine935 LRRK2 phosphorylation in striatal and cerebrocortical synaptosomes.Pharmacology research & perspectives · 2019Article
- Crosstalk between presynaptic trafficking and autophagy in Parkinson's disease.Neurobiology of disease · 2019Review
- Personalized medicine in Parkinson's disease: Time to be precise.Movement disorders : official journal of the Movement Disorder Society · 2017Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
introductionMutations in leucine-rich repeat kinase 2 (LRRK2) are the most prevalent cause of familial and sporadic Parkinson's disease (PD). Because most pathogenic LRRK2 mutations result in enhanced kinase activity, it suggests that LRRK2 inhibitors may serve as a potential treatment for PD. To evaluate whether LRRK2 inhibitors are effective therapies for PD, it is crucial to know whether LRRK2 inhibitors will affect dopaminergic (DAergic) neurotransmission. However, to date, there is no study to investigate the impact of LRRK2 inhibitors on DAergic neurotransmission.
aimsTo address this gap in knowledge, we examined the effects of three types of LRRK2 inhibitors (LRRK2-IN-1, GSK2578215A, and GNE-7915) on dopamine (DA) release in the dorsal striatum using fast-scan cyclic voltammetry and DA neuron firing in the substantia nigra pars compacta (SNpc) using patch clamp in mouse brain slices.
resultsWe found that LRRK2-IN-1 at a concentration higher than 1 μM causes off-target effects and decreases DA release, whereas GSK2578215A and GNE-7915 do not. All three inhibitors at 1 μM have no effect on DA release and DA neuron firing rate. We have further assessed the effects of the inhibitors in two preclinical LRRK2 mouse models (i.e., BAC transgenic hG2019S and hR1441G) and demonstrated that GNE-7915 enhances DA release and synaptic vesicle mobilization/recycling.
conclusionGNE-7915 can be validated for further therapeutic development for PD.
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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.