ArticleHuman molecular genetics2014
Abnormal visual gain control in a Parkinson's disease model.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 50 citations in OpenAlex.
- Lysosomal TPC2 channels disrupt Ca2+ entry and dopaminergic function in models of LRRK2-Parkinson's disease.The Journal of cell biology · 2025Article
- Knocking out the LRRK2 gene increases sensitivity to wavelength information in rats.Scientific reports · 2024Article
- Article
- Choroid and choriocapillaris changes in early-stage Parkinson's disease: a swept-source optical coherence tomography angiography-based cross-sectional study.Alzheimer's research & therapy · 2022Article
- Presynaptic accumulation of α-synuclein causes synaptopathy and progressive neurodegeneration inBrain communications · 2021Article
- Retinal Degeneration: A Window to Understand the Origin and Progression of Parkinson's Disease?Frontiers in neuroscience · 2021Review
- Classification of α-synuclein-induced changes in the AAV α-synuclein rat model of Parkinson's disease using electrophysiological measurements of visual processing.Scientific reports · 2020Article
- Article
- Vitamin BCell research · 2019Article
- Altered dynamics of visual contextual interactions in Parkinson's disease.NPJ Parkinson's disease · 2019Article
- Autism sensory dysfunction in an evolutionarily conserved system.Proceedings. Biological sciences · 2018Article
- Circadian Rhythm Abnormalities in Parkinson's Disease from Humans to Flies and Back.International journal of molecular sciences · 2018Review
- Review
- Abnormal visual gain control and excitotoxicity in early-onset Parkinson's disease Drosophila models.Journal of neurophysiology · 2018Article
- A perceptive plus in Parkinson's disease.Movement disorders : official journal of the Movement Disorder Society · 2018Article
- Circadian Rhythms in Visual Responsiveness in the Behaviorally Arrhythmic Drosophila Clock Mutant ClkJournal of biological rhythms · 2017Article
- Selective LRRK2 kinase inhibition reduces phosphorylation of endogenous Rab10 and Rab12 in human peripheral mononuclear blood cells.Scientific reports · 2017Article
- Targeted kinase inhibition relieves slowness and tremor in aNPJ Parkinson's disease · 2017Article
- Evidence for an Optimal Algorithm Underlying Signal Combination in Human Visual Cortex.Cerebral cortex (New York, N.Y. : 1991) · 2017Article
- Computational approaches for understanding the diagnosis and treatment of Parkinson's disease.IET systems biology · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Our understanding of Parkinson's disease (PD) has been revolutionized by the discovery of disease-causing genetic mutations. The most common of these is the G2019S mutation in the LRRK2 kinase gene, which leads to increased kinase activity. However, the link between increased kinase activity and PD is unclear. Previously, we showed that dopaminergic expression of the human LRRK2-G2019S transgene in flies led to an activity-dependent loss of vision in older animals and we hypothesized that this may have been preceded by a failure to regulate neuronal activity correctly in younger animals. To test this hypothesis, we used a sensitive measure of visual function based on frequency-tagged steady-state visually evoked potentials. Spectral analysis allowed us to identify signals from multiple levels of the fly visual system and wild-type visual response curves were qualitatively similar to those from human cortex. Dopaminergic expression of hLRRK2-G2019S increased contrast sensitivity throughout the retinal network. To test whether this was due to increased kinase activity, we fed Drosophila with kinase inhibitors targeted at LRRK2. Contrast sensitivity in both day 1 and day 14 flies was normalized by a novel LRRK2 kinase inhibitor 'BMPPB-32'. Biochemical and cellular assays suggested that BMPPB-32 would be a more specific kinase inhibitor than LRRK2-IN-1. We confirmed this in vivo, finding that dLRRK(-) null flies show large off-target effects with LRRK2-IN-1 but not BMPPB-32. Our data link the increased Kinase activity of the G2019S-LRRK2 mutation to neuronal dysfunction and demonstrate the power of the Drosophila visual system in assaying the neurological effects of genetic diseases and therapies.
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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.