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Cell cycle inhibitors protect motor neurons in an organoid model of Spinal Muscular Atrophy
Spinal Muscular Atrophy (SMA) is caused by genetic mutations in the SMN1 gene, resulting in drastically reduced levels of Survival of Motor Neuron (SMN) protein. Although SMN is ubiquitously expressed, spinal motor neurons are one of the most affected cell types. Previous studies have identified pat...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204135/ https://www.ncbi.nlm.nih.gov/pubmed/30368521 http://dx.doi.org/10.1038/s41419-018-1081-0 |
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author | Hor, Jin Hui Soh, Eunice Shi-Yi Tan, Li Yi Lim, Valerie Jing Wen Santosa, Munirah Mohamad Winanto Ho, Beatrice Xuan Fan, Yong Soh, Boon-Seng Ng, Shi-Yan |
author_facet | Hor, Jin Hui Soh, Eunice Shi-Yi Tan, Li Yi Lim, Valerie Jing Wen Santosa, Munirah Mohamad Winanto Ho, Beatrice Xuan Fan, Yong Soh, Boon-Seng Ng, Shi-Yan |
author_sort | Hor, Jin Hui |
collection | PubMed |
description | Spinal Muscular Atrophy (SMA) is caused by genetic mutations in the SMN1 gene, resulting in drastically reduced levels of Survival of Motor Neuron (SMN) protein. Although SMN is ubiquitously expressed, spinal motor neurons are one of the most affected cell types. Previous studies have identified pathways uniquely activated in SMA motor neurons, including a hyperactivated ER stress pathway, neuronal hyperexcitability, and defective spliceosomes. To investigate why motor neurons are more affected than other neural types, we developed a spinal organoid model of SMA. We demonstrate overt motor neuron degeneration in SMA spinal organoids, and this degeneration can be prevented using a small molecule inhibitor of CDK4/6, indicating that spinal organoids are an ideal platform for therapeutic discovery. |
format | Online Article Text |
id | pubmed-6204135 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-62041352018-10-29 Cell cycle inhibitors protect motor neurons in an organoid model of Spinal Muscular Atrophy Hor, Jin Hui Soh, Eunice Shi-Yi Tan, Li Yi Lim, Valerie Jing Wen Santosa, Munirah Mohamad Winanto Ho, Beatrice Xuan Fan, Yong Soh, Boon-Seng Ng, Shi-Yan Cell Death Dis Article Spinal Muscular Atrophy (SMA) is caused by genetic mutations in the SMN1 gene, resulting in drastically reduced levels of Survival of Motor Neuron (SMN) protein. Although SMN is ubiquitously expressed, spinal motor neurons are one of the most affected cell types. Previous studies have identified pathways uniquely activated in SMA motor neurons, including a hyperactivated ER stress pathway, neuronal hyperexcitability, and defective spliceosomes. To investigate why motor neurons are more affected than other neural types, we developed a spinal organoid model of SMA. We demonstrate overt motor neuron degeneration in SMA spinal organoids, and this degeneration can be prevented using a small molecule inhibitor of CDK4/6, indicating that spinal organoids are an ideal platform for therapeutic discovery. Nature Publishing Group UK 2018-10-27 /pmc/articles/PMC6204135/ /pubmed/30368521 http://dx.doi.org/10.1038/s41419-018-1081-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Hor, Jin Hui Soh, Eunice Shi-Yi Tan, Li Yi Lim, Valerie Jing Wen Santosa, Munirah Mohamad Winanto Ho, Beatrice Xuan Fan, Yong Soh, Boon-Seng Ng, Shi-Yan Cell cycle inhibitors protect motor neurons in an organoid model of Spinal Muscular Atrophy |
title | Cell cycle inhibitors protect motor neurons in an organoid model of Spinal Muscular Atrophy |
title_full | Cell cycle inhibitors protect motor neurons in an organoid model of Spinal Muscular Atrophy |
title_fullStr | Cell cycle inhibitors protect motor neurons in an organoid model of Spinal Muscular Atrophy |
title_full_unstemmed | Cell cycle inhibitors protect motor neurons in an organoid model of Spinal Muscular Atrophy |
title_short | Cell cycle inhibitors protect motor neurons in an organoid model of Spinal Muscular Atrophy |
title_sort | cell cycle inhibitors protect motor neurons in an organoid model of spinal muscular atrophy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204135/ https://www.ncbi.nlm.nih.gov/pubmed/30368521 http://dx.doi.org/10.1038/s41419-018-1081-0 |
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