Creatine mitigates neurogenesis impairment caused by defective DcpS decapping
Abstract Biallelic mutations in the DCPS gene disrupting the decapping activity of the scavenger decapping protein DcpS, leads to neurodevelopmental deficiencies and intellectual disability. However, the molecular basis for the neurogenesis defects in these individuals remains unknown. Here we show...
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Nature Portfolio
2025-05-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-02961-5 |
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| author | Jun Yang Geeta Palsule Xinfu Jiao Jaime S. Messenger Ronald P. Hart Megerditch Kiledjian |
| author_facet | Jun Yang Geeta Palsule Xinfu Jiao Jaime S. Messenger Ronald P. Hart Megerditch Kiledjian |
| author_sort | Jun Yang |
| collection | DOAJ |
| description | Abstract Biallelic mutations in the DCPS gene disrupting the decapping activity of the scavenger decapping protein DcpS, leads to neurodevelopmental deficiencies and intellectual disability. However, the molecular basis for the neurogenesis defects in these individuals remains unknown. Here we show that cells derived from individuals with a DCPS mutation harbor a creatine deficiency and a corresponding elevation of the creatine precursor, guanidinoacetate (GAA). The altered metabolite levels are a consequence of a reduction in both the mRNA and protein levels for the enzyme that converts GAA into creatine, guanidinoacetate methyltransferase. Importantly, the compromised neurogenesis and neurite outgrowth phenotypes observed during the differentiation of DcpS mutant patient derived induced pluripotent stem cells into neurons was reversed upon supplementation of creatine monohydrate. These findings suggest creatine deficiency as an underlying factor for the neurogenetic defect detected in DcpS mutant cells and a potential driver of the neurological deficiencies in affected individuals. |
| format | Article |
| id | doaj-art-cd28d0ed6eb044b5bdefa0da68888c24 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-cd28d0ed6eb044b5bdefa0da68888c242025-08-20T01:53:11ZengNature PortfolioScientific Reports2045-23222025-05-0115111010.1038/s41598-025-02961-5Creatine mitigates neurogenesis impairment caused by defective DcpS decappingJun Yang0Geeta Palsule1Xinfu Jiao2Jaime S. Messenger3Ronald P. Hart4Megerditch Kiledjian5Department of Cell Biology and Neuroscience, Rutgers, The State University of New JerseyDepartment of Cell Biology and Neuroscience, Rutgers, The State University of New JerseyDepartment of Cell Biology and Neuroscience, Rutgers, The State University of New JerseyDepartment of Cell Biology and Neuroscience, Rutgers, The State University of New JerseyDepartment of Cell Biology and Neuroscience, Rutgers, The State University of New JerseyDepartment of Cell Biology and Neuroscience, Rutgers, The State University of New JerseyAbstract Biallelic mutations in the DCPS gene disrupting the decapping activity of the scavenger decapping protein DcpS, leads to neurodevelopmental deficiencies and intellectual disability. However, the molecular basis for the neurogenesis defects in these individuals remains unknown. Here we show that cells derived from individuals with a DCPS mutation harbor a creatine deficiency and a corresponding elevation of the creatine precursor, guanidinoacetate (GAA). The altered metabolite levels are a consequence of a reduction in both the mRNA and protein levels for the enzyme that converts GAA into creatine, guanidinoacetate methyltransferase. Importantly, the compromised neurogenesis and neurite outgrowth phenotypes observed during the differentiation of DcpS mutant patient derived induced pluripotent stem cells into neurons was reversed upon supplementation of creatine monohydrate. These findings suggest creatine deficiency as an underlying factor for the neurogenetic defect detected in DcpS mutant cells and a potential driver of the neurological deficiencies in affected individuals.https://doi.org/10.1038/s41598-025-02961-5DcpSDecappingNeurogenesisNeuritogenesisCreatine supplementation |
| spellingShingle | Jun Yang Geeta Palsule Xinfu Jiao Jaime S. Messenger Ronald P. Hart Megerditch Kiledjian Creatine mitigates neurogenesis impairment caused by defective DcpS decapping Scientific Reports DcpS Decapping Neurogenesis Neuritogenesis Creatine supplementation |
| title | Creatine mitigates neurogenesis impairment caused by defective DcpS decapping |
| title_full | Creatine mitigates neurogenesis impairment caused by defective DcpS decapping |
| title_fullStr | Creatine mitigates neurogenesis impairment caused by defective DcpS decapping |
| title_full_unstemmed | Creatine mitigates neurogenesis impairment caused by defective DcpS decapping |
| title_short | Creatine mitigates neurogenesis impairment caused by defective DcpS decapping |
| title_sort | creatine mitigates neurogenesis impairment caused by defective dcps decapping |
| topic | DcpS Decapping Neurogenesis Neuritogenesis Creatine supplementation |
| url | https://doi.org/10.1038/s41598-025-02961-5 |
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