ArticleMolecular neurobiology2018
Role of Dopamine D2/D3 Receptors in Development, Plasticity, and Neuroprotection in Human iPSC-Derived Midbrain Dopaminergic Neurons.
Article in Molecular neurobiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Pooled it
- LRRK2-Mediated Neuroinflammation-Induced Neuronal Dysfunctions in a Parkinson's and Alzheimer's Disease Cellular Model.Biomolecules · 2025Article
- The Neuroanatomy of Induced Pluripotent Stem Cells: In Vitro Models of Subcortical Nuclei in Neurodegenerative Disorders.Current issues in molecular biology · 2024Review
- Neuroprotective effects of quinpirole on lithium chloride pilocarpine-induced epilepsy in rats and its underlying mechanisms.European journal of medical research · 2024Article
- Quinpirole ameliorates nigral dopaminergic neuron damage in Parkinson's disease mouse model through activating GHS-R1a/DActa pharmacologica Sinica · 2023Article
- Article
- Combining NGN2 programming and dopaminergic patterning for a rapid and efficient generation of hiPSC-derived midbrain neurons.Scientific reports · 2022Article
- Induced pluripotent stem cells for defining Parkinsonian patient subtypes: a further step toward precision medicine.Neural regeneration research · 2022Article
- Structural Plasticity of Dopaminergic Neurons Requires the Activation of the D3R-nAChR Heteromer and the PI3K-ERK1/2/Akt-Induced Expression of c-Fos and p70S6K Signaling Pathway.Molecular neurobiology · 2022Article
- α-Synuclein-induced dysregulation of neuronal activity contributes to murine dopamine neuron vulnerability.NPJ Parkinson's disease · 2021Article
- Extracellular clusterin limits the uptake of α-synuclein fibrils by murine and human astrocytes.Glia · 2021Article
- Dopamine D1 + D3 receptor density may correlate with parkinson disease clinical features.Annals of clinical and translational neurology · 2021Article
- Dopamine D3 Receptor Heteromerization: Implications for Neuroplasticity and Neuroprotection.Biomolecules · 2020Review
- Dopamine D3 receptor: A neglected participant in Parkinson Disease pathogenesis and treatment?Ageing research reviews · 2020Review
- Toward Generating Subtype-Specific Mesencephalic Dopaminergic NeuronsFrontiers in cell and developmental biology · 2020Review
- Living in Promiscuity: The Multiple Partners of Alpha-Synuclein at the Synapse in Physiology and Pathology.International journal of molecular sciences · 2019Review
- Exploring pre-degenerative alterations in humans using induced pluripotent stem cell-derived dopaminergic neurons.Neural regeneration research · 2017Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The role of dopamine D2 and D3 receptors (D2R/D3R), located on midbrain dopaminergic (DA) neurons, in the regulation of DA synthesis and release and in DA neuron homeostasis has been extensively investigated in rodent animal models. By contrast, the properties of D2R/D3R in human DA neurons have not been elucidated yet. On this line, the use of human-induced pluripotent stem cells (hiPSCs) for producing any types of cells has offered the innovative opportunity for investigating the human neuronal phenotypes at the molecular levels. In the present study, hiPSCs generated from human dermal fibroblasts were used to produce midbrain DA (mDA) neurons, expressing the proper set of genes and proteins typical of authentic, terminally differentiated DA neurons. In this model, the expression and the functional properties of the human D2R/D3R were investigated with a combination of biochemical and functional techniques. We observed that in hiPSC-derived mDA neurons, the activation of D2R/D3R promotes the proliferation of neuronal progenitor cells. In addition, we found that D2R/D3R activation inhibits nicotine-stimulated DA release and exerts neurotrophic effects on mDA neurons that likely occur via the activation of PI3K-dependent mechanisms. Furthermore, D2R/D3R stimulation counteracts both the aggregation of alpha-synuclein induced by glucose deprivation and the associated neuronal damage affecting both the soma and the dendrites of mDA neurons. Taken together, these data point to the D2R/D3R-related signaling events as a biochemical pathway crucial for supporting both neuronal development and survival and protection of human DA neurons.
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Registered trials
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