Exploring <i>RNF213</i> in Ischemic Stroke and Moyamoya Disease: From Cellular Models to Clinical Insights
Advances in stroke genetics have highlighted the critical role of rare genetic variants in cerebrovascular diseases, with <i>RNF213</i> emerging as a key player in ischemic stroke and Moyamoya disease (MMD). Initially identified as the primary susceptibility gene for MMD, <i>RNF213...
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2024-12-01
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| Online Access: | https://www.mdpi.com/2227-9059/13/1/17 |
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| author | Benjamin Y. Q. Tan Charlene H. P. Kok Megan B. J. Ng Shaun Loong Eric Jou Leonard L. L. Yeo Weiping Han Christopher D. Anderson Chiea Chuen Khor Poh San Lai |
| author_facet | Benjamin Y. Q. Tan Charlene H. P. Kok Megan B. J. Ng Shaun Loong Eric Jou Leonard L. L. Yeo Weiping Han Christopher D. Anderson Chiea Chuen Khor Poh San Lai |
| author_sort | Benjamin Y. Q. Tan |
| collection | DOAJ |
| description | Advances in stroke genetics have highlighted the critical role of rare genetic variants in cerebrovascular diseases, with <i>RNF213</i> emerging as a key player in ischemic stroke and Moyamoya disease (MMD). Initially identified as the primary susceptibility gene for MMD, <i>RNF213</i>—notably the p.R4810K variant—has been strongly linked to intracranial artery stenosis (ICAS) and various ischemic stroke subtypes, particularly in East Asian populations. This gene encodes an E3 ubiquitin ligase with diverse roles in angiogenesis, vascular remodeling, lipid metabolism, and cerebral blood flow regulation, yet its exact mechanisms in cerebrovascular pathology remain incompletely understood. This review synthesizes findings from genetic studies, as well as cellular and animal models, to provide a holistic understanding of <i>RNF213</i>’s involvement in cerebrovascular diseases. Key mechanisms by which <i>RNF213</i> variants contribute to disease pathogenesis are explored, alongside discussions on their clinical utility as biomarkers and therapeutic targets. Additionally, we address the gene’s implications for disease prediction, risk assessment, and cascade screening. By integrating evidence across disciplines, this review identifies critical knowledge gaps, including the biological pathways underlying <i>RNF213</i>’s pathogenicity. These insights lay the groundwork for future research and underscore the potential of <i>RNF213</i> in driving personalized approaches to cerebrovascular disease management. |
| format | Article |
| id | doaj-art-a6dcae3d8e6848aaa1c424bb88d328b6 |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-a6dcae3d8e6848aaa1c424bb88d328b62025-01-24T13:23:43ZengMDPI AGBiomedicines2227-90592024-12-011311710.3390/biomedicines13010017Exploring <i>RNF213</i> in Ischemic Stroke and Moyamoya Disease: From Cellular Models to Clinical InsightsBenjamin Y. Q. Tan0Charlene H. P. Kok1Megan B. J. Ng2Shaun Loong3Eric Jou4Leonard L. L. Yeo5Weiping Han6Christopher D. Anderson7Chiea Chuen Khor8Poh San Lai9Division of Neurology, Department of Medicine, National University Hospital, Singapore 119074, SingaporeFaculty of Medicine, Imperial College London, London SW7 2AZ, UKDivision of Neurology, Department of Medicine, National University Hospital, Singapore 119074, SingaporeDepartment of Medicine, Yong Loo Lin School of Medicine, Singapore 117597, SingaporeDepartment of Oncology, University of Oxford, Oxford OX3 7DQ, UKDivision of Neurology, Department of Medicine, National University Hospital, Singapore 119074, SingaporeInstitute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore 138632, SingaporeProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USAGenome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR), Singapore 138632, SingaporeDepartment of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, SingaporeAdvances in stroke genetics have highlighted the critical role of rare genetic variants in cerebrovascular diseases, with <i>RNF213</i> emerging as a key player in ischemic stroke and Moyamoya disease (MMD). Initially identified as the primary susceptibility gene for MMD, <i>RNF213</i>—notably the p.R4810K variant—has been strongly linked to intracranial artery stenosis (ICAS) and various ischemic stroke subtypes, particularly in East Asian populations. This gene encodes an E3 ubiquitin ligase with diverse roles in angiogenesis, vascular remodeling, lipid metabolism, and cerebral blood flow regulation, yet its exact mechanisms in cerebrovascular pathology remain incompletely understood. This review synthesizes findings from genetic studies, as well as cellular and animal models, to provide a holistic understanding of <i>RNF213</i>’s involvement in cerebrovascular diseases. Key mechanisms by which <i>RNF213</i> variants contribute to disease pathogenesis are explored, alongside discussions on their clinical utility as biomarkers and therapeutic targets. Additionally, we address the gene’s implications for disease prediction, risk assessment, and cascade screening. By integrating evidence across disciplines, this review identifies critical knowledge gaps, including the biological pathways underlying <i>RNF213</i>’s pathogenicity. These insights lay the groundwork for future research and underscore the potential of <i>RNF213</i> in driving personalized approaches to cerebrovascular disease management.https://www.mdpi.com/2227-9059/13/1/17strokemoyamoya<i>RNF213</i>geneticsintracranial stenosisintracranial atherosclerotic disease |
| spellingShingle | Benjamin Y. Q. Tan Charlene H. P. Kok Megan B. J. Ng Shaun Loong Eric Jou Leonard L. L. Yeo Weiping Han Christopher D. Anderson Chiea Chuen Khor Poh San Lai Exploring <i>RNF213</i> in Ischemic Stroke and Moyamoya Disease: From Cellular Models to Clinical Insights Biomedicines stroke moyamoya <i>RNF213</i> genetics intracranial stenosis intracranial atherosclerotic disease |
| title | Exploring <i>RNF213</i> in Ischemic Stroke and Moyamoya Disease: From Cellular Models to Clinical Insights |
| title_full | Exploring <i>RNF213</i> in Ischemic Stroke and Moyamoya Disease: From Cellular Models to Clinical Insights |
| title_fullStr | Exploring <i>RNF213</i> in Ischemic Stroke and Moyamoya Disease: From Cellular Models to Clinical Insights |
| title_full_unstemmed | Exploring <i>RNF213</i> in Ischemic Stroke and Moyamoya Disease: From Cellular Models to Clinical Insights |
| title_short | Exploring <i>RNF213</i> in Ischemic Stroke and Moyamoya Disease: From Cellular Models to Clinical Insights |
| title_sort | exploring i rnf213 i in ischemic stroke and moyamoya disease from cellular models to clinical insights |
| topic | stroke moyamoya <i>RNF213</i> genetics intracranial stenosis intracranial atherosclerotic disease |
| url | https://www.mdpi.com/2227-9059/13/1/17 |
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