Targeting NMDA receptors in neuropsychiatric disorders by drug screening on human neurons derived from pluripotent stem cells
Abstract NMDA receptors (NMDARs), a prominent subtype of glutamatergic receptors, are implicated in the pathogenesis and development of neuropsychiatric disorders such as epilepsy, intellectual disability, autism spectrum disorder, and schizophrenia, and are therefore a potential therapeutic target...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-06-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-022-02010-z |
| _version_ | 1828335598911356928 |
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| author | Wenbo Zhang P. Joel Ross James Ellis Michael W. Salter |
| author_facet | Wenbo Zhang P. Joel Ross James Ellis Michael W. Salter |
| author_sort | Wenbo Zhang |
| collection | DOAJ |
| description | Abstract NMDA receptors (NMDARs), a prominent subtype of glutamatergic receptors, are implicated in the pathogenesis and development of neuropsychiatric disorders such as epilepsy, intellectual disability, autism spectrum disorder, and schizophrenia, and are therefore a potential therapeutic target in treating these disorders. Neurons derived from induced pluripotent stem cells (iPSCs) have provided the opportunity to investigate human NMDARs in their native environment. In this review, we describe the expression, function, and regulation of NMDARs in human iPSC-derived neurons and discuss approaches for utilizing human neurons for identifying potential drugs that target NMDARs in the treatment of neuropsychiatric disorders. A challenge in studying NMDARs in human iPSC-derived neurons is a predominance of those receptors containing the GluN2B subunit and low synaptic expression, suggesting a relatively immature phenotype of these neurons and delayed development of functional NMDARs. We outline potential approaches for improving neuronal maturation of human iPSC-derived neurons and accelerating the functional expression of NMDARs. Acceleration of functional expression of NMDARs in human iPSC-derived neurons will improve the modeling of neuropsychiatric disorders and facilitate the discovery and development of novel therapeutics targeting NMDARs for the treatment of these disorders. |
| first_indexed | 2024-04-13T21:49:31Z |
| format | Article |
| id | doaj.art-eb0a77b8928c420db7d3b0dc9e90a980 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-04-13T21:49:31Z |
| publishDate | 2022-06-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-eb0a77b8928c420db7d3b0dc9e90a9802022-12-22T02:28:27ZengNature Publishing GroupTranslational Psychiatry2158-31882022-06-0112111110.1038/s41398-022-02010-zTargeting NMDA receptors in neuropsychiatric disorders by drug screening on human neurons derived from pluripotent stem cellsWenbo Zhang0P. Joel Ross1James Ellis2Michael W. Salter3Program in Neurosciences & Mental Health, The Hospital for Sick ChildrenBiology Department, University of Prince Edward IslandProgram in Developmental & Stem Cell Biology, The Hospital for Sick ChildrenProgram in Neurosciences & Mental Health, The Hospital for Sick ChildrenAbstract NMDA receptors (NMDARs), a prominent subtype of glutamatergic receptors, are implicated in the pathogenesis and development of neuropsychiatric disorders such as epilepsy, intellectual disability, autism spectrum disorder, and schizophrenia, and are therefore a potential therapeutic target in treating these disorders. Neurons derived from induced pluripotent stem cells (iPSCs) have provided the opportunity to investigate human NMDARs in their native environment. In this review, we describe the expression, function, and regulation of NMDARs in human iPSC-derived neurons and discuss approaches for utilizing human neurons for identifying potential drugs that target NMDARs in the treatment of neuropsychiatric disorders. A challenge in studying NMDARs in human iPSC-derived neurons is a predominance of those receptors containing the GluN2B subunit and low synaptic expression, suggesting a relatively immature phenotype of these neurons and delayed development of functional NMDARs. We outline potential approaches for improving neuronal maturation of human iPSC-derived neurons and accelerating the functional expression of NMDARs. Acceleration of functional expression of NMDARs in human iPSC-derived neurons will improve the modeling of neuropsychiatric disorders and facilitate the discovery and development of novel therapeutics targeting NMDARs for the treatment of these disorders.https://doi.org/10.1038/s41398-022-02010-z |
| spellingShingle | Wenbo Zhang P. Joel Ross James Ellis Michael W. Salter Targeting NMDA receptors in neuropsychiatric disorders by drug screening on human neurons derived from pluripotent stem cells Translational Psychiatry |
| title | Targeting NMDA receptors in neuropsychiatric disorders by drug screening on human neurons derived from pluripotent stem cells |
| title_full | Targeting NMDA receptors in neuropsychiatric disorders by drug screening on human neurons derived from pluripotent stem cells |
| title_fullStr | Targeting NMDA receptors in neuropsychiatric disorders by drug screening on human neurons derived from pluripotent stem cells |
| title_full_unstemmed | Targeting NMDA receptors in neuropsychiatric disorders by drug screening on human neurons derived from pluripotent stem cells |
| title_short | Targeting NMDA receptors in neuropsychiatric disorders by drug screening on human neurons derived from pluripotent stem cells |
| title_sort | targeting nmda receptors in neuropsychiatric disorders by drug screening on human neurons derived from pluripotent stem cells |
| url | https://doi.org/10.1038/s41398-022-02010-z |
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