ArticleJCI insight2019
Age-dependent nigral dopaminergic neurodegeneration and α-synuclein accumulation in RGS6-deficient mice.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 26 citations in OpenAlex.
- RGS6 regulates Kappa opioid receptor-mediated antinociceptive behaviors.Neuropharmacology · 2026Article
- Regulator of G Protein Signaling 6 Negatively Regulates Platelet Activation and Arterial Thrombosis in Mice.bioRxiv : the preprint server for biology · 2026Article
- Multiplex neurodegeneration proteotoxicity platform reveals DNAJB6 promotes non-toxic FUS condensate gelation and inhibits neurotoxicity.Nature communications · 2025Article
- A Multimodal Atlas Reveals the Anatomical Distribution of Medium Spiny Neuron Subtypes and a Novel RGS6+ Population in the Primate Striatum.bioRxiv : the preprint server for biology · 2025Article
- Molecular signatures of regional vulnerability to tauopathy in excitatory cortical neurons.Acta neuropathologica · 2025Article
- Regulator of G protein signaling 6 (RGS6) in dopamine neurons promotes EtOH seeking, behavioral reward, and susceptibility to relapse.Psychopharmacology · 2024Article
- Article
- A splice acceptor variant in RGS6 associated with intellectual disability, microcephaly, and cataracts disproportionately promotes expression of a subset of RGS6 isoforms.Journal of human genetics · 2024Article
- Behavioral analysis of motor and non-motor impairment in rodent models of Parkinson's disease.Frontiers in aging neuroscience · 2024Review
- Genes positively regulated by Mef2c in cortical neurons are enriched for common genetic variation associated with IQ and educational attainment.Human molecular genetics · 2023Article
- The Evolving Role of Animal Models in the Discovery and Development of Novel Treatments for Psychiatric Disorders.Advances in neurobiology · 2023Article
- Aging, Parkinson's Disease, and Models: What Are the Challenges?Aging biology · 2023Article
- RGS6 Drives Spinal Cord Injury by Inhibiting AMPK Pathway in Mice.Disease markers · 2022Article
- Exploring the Genomic Patterns in Human and Mouse Cerebellums Via Single-Cell Sequencing and Machine Learning Method.Frontiers in genetics · 2022Article
- Quantifying Levels of Dopaminergic Neuron Morphological Alteration and Degeneration in Caenorhabditis elegans.Journal of visualized experiments : JoVE · 2021Article
- The Biology and Pathobiology of Glutamatergic, Cholinergic, and Dopaminergic Signaling in the Aging Brain.Frontiers in aging neuroscience · 2021Review
- RGS Proteins as Critical Regulators of Motor Function and Their Implications in Parkinson's Disease.Molecular pharmacology · 2020Review
- Dopamine D2 autoreceptor interactome: Targeting the receptor complex as a strategy for treatment of substance use disorder.Pharmacology & therapeutics · 2020Review
- Midbrain Dopaminergic Neuron Development at the Single Cell Level:Frontiers in cell and developmental biology · 2020Review
- Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Parkinson's is primarily a non-familial, age-related disorder caused by α-synuclein accumulation and the progressive loss of dopamine neurons in the substantia nigra pars compacta (SNc). G protein-coupled receptor (GPCR)-cAMP signaling has been linked to a reduction in human Parkinson's incidence and α-synuclein expression. Neuronal cAMP levels are controlled by GPCRs coupled to Gs or Gi/o, which increase or decrease cAMP, respectively. Regulator of G protein signaling 6 (RGS6) powerfully inhibits Gi/o signaling. Therefore, we hypothesized that RGS6 suppresses D2 autoreceptor- Gi/o signaling in SNc dopamine neurons promoting neuronal survival and reducing α-synuclein expression. Here we provide novel evidence that RGS6 critically suppresses late-age-onset SNc dopamine neuron loss and α-synuclein accumulation. RGS6 is restrictively expressed in human SNc dopamine neurons and, despite their loss in Parkinson's, all surviving neurons express RGS6. RGS6-/- mice exhibit hyperactive D2 autoreceptors with reduced cAMP signaling in SNc dopamine neurons. Importantly, RGS6-/- mice recapitulate key sporadic Parkinson's hallmarks, including: SNc dopamine neuron loss, reduced nigrostriatal dopamine, motor deficits, and α-synuclein accumulation. To our knowledge, Rgs6 is the only gene whose loss phenocopies these features of human Parkinson's. Therefore, RGS6 is a key regulator of D2R-Gi/o signaling in SNc dopamine neurons, protecting against Parkinson's neurodegeneration and α-synuclein accumulation.
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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.