Kuwanon V inhibits proliferation, promotes cell survival and increases neurogenesis of neural stem cells.
Neural stem cells (NSCs) have the ability to proliferate and differentiate into neurons and glia. Regulation of NSC fate by small molecules is important for the generation of a certain type of cell. The identification of small molecules that can induce new neurons from NSCs could facilitate regenera...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0118188&type=printable |
| _version_ | 1826586562310176768 |
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| author | Sun-Young Kong Min-Hye Park Mina Lee Jae-Ouk Kim Ha-Rim Lee Byung Woo Han Clive N Svendsen Sang Hyun Sung Hyun-Jung Kim |
| author_facet | Sun-Young Kong Min-Hye Park Mina Lee Jae-Ouk Kim Ha-Rim Lee Byung Woo Han Clive N Svendsen Sang Hyun Sung Hyun-Jung Kim |
| author_sort | Sun-Young Kong |
| collection | DOAJ |
| description | Neural stem cells (NSCs) have the ability to proliferate and differentiate into neurons and glia. Regulation of NSC fate by small molecules is important for the generation of a certain type of cell. The identification of small molecules that can induce new neurons from NSCs could facilitate regenerative medicine and drug development for neurodegenerative diseases. In this study, we screened natural compounds to identify molecules that are effective on NSC cell fate determination. We found that Kuwanon V (KWV), which was isolated from the mulberry tree (Morus bombycis) root, increased neurogenesis in rat NSCs. In addition, during NSC differentiation, KWV increased cell survival and inhibited cell proliferation as shown by 5-bromo-2-deoxyuridine pulse experiments, Ki67 immunostaining and neurosphere forming assays. Interestingly, KWV enhanced neuronal differentiation and decreased NSC proliferation even in the presence of mitogens such as epidermal growth factor and fibroblast growth factor 2. KWV treatment of NSCs reduced the phosphorylation of extracellular signal-regulated kinase 1/2, increased mRNA expression levels of the cyclin-dependent kinase inhibitor p21, down-regulated Notch/Hairy expression levels and up-regulated microRNA miR-9, miR-29a and miR-181a. Taken together, our data suggest that KWV modulates NSC fate to induce neurogenesis, and it may be considered as a new drug candidate that can regenerate or protect neurons in neurodegenerative diseases. |
| first_indexed | 2024-12-10T07:44:00Z |
| format | Article |
| id | doaj.art-d9383fd11828498585838070399f9a96 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2025-03-14T16:11:31Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d9383fd11828498585838070399f9a962025-02-23T05:32:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01102e011818810.1371/journal.pone.0118188Kuwanon V inhibits proliferation, promotes cell survival and increases neurogenesis of neural stem cells.Sun-Young KongMin-Hye ParkMina LeeJae-Ouk KimHa-Rim LeeByung Woo HanClive N SvendsenSang Hyun SungHyun-Jung KimNeural stem cells (NSCs) have the ability to proliferate and differentiate into neurons and glia. Regulation of NSC fate by small molecules is important for the generation of a certain type of cell. The identification of small molecules that can induce new neurons from NSCs could facilitate regenerative medicine and drug development for neurodegenerative diseases. In this study, we screened natural compounds to identify molecules that are effective on NSC cell fate determination. We found that Kuwanon V (KWV), which was isolated from the mulberry tree (Morus bombycis) root, increased neurogenesis in rat NSCs. In addition, during NSC differentiation, KWV increased cell survival and inhibited cell proliferation as shown by 5-bromo-2-deoxyuridine pulse experiments, Ki67 immunostaining and neurosphere forming assays. Interestingly, KWV enhanced neuronal differentiation and decreased NSC proliferation even in the presence of mitogens such as epidermal growth factor and fibroblast growth factor 2. KWV treatment of NSCs reduced the phosphorylation of extracellular signal-regulated kinase 1/2, increased mRNA expression levels of the cyclin-dependent kinase inhibitor p21, down-regulated Notch/Hairy expression levels and up-regulated microRNA miR-9, miR-29a and miR-181a. Taken together, our data suggest that KWV modulates NSC fate to induce neurogenesis, and it may be considered as a new drug candidate that can regenerate or protect neurons in neurodegenerative diseases.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0118188&type=printable |
| spellingShingle | Sun-Young Kong Min-Hye Park Mina Lee Jae-Ouk Kim Ha-Rim Lee Byung Woo Han Clive N Svendsen Sang Hyun Sung Hyun-Jung Kim Kuwanon V inhibits proliferation, promotes cell survival and increases neurogenesis of neural stem cells. PLoS ONE |
| title | Kuwanon V inhibits proliferation, promotes cell survival and increases neurogenesis of neural stem cells. |
| title_full | Kuwanon V inhibits proliferation, promotes cell survival and increases neurogenesis of neural stem cells. |
| title_fullStr | Kuwanon V inhibits proliferation, promotes cell survival and increases neurogenesis of neural stem cells. |
| title_full_unstemmed | Kuwanon V inhibits proliferation, promotes cell survival and increases neurogenesis of neural stem cells. |
| title_short | Kuwanon V inhibits proliferation, promotes cell survival and increases neurogenesis of neural stem cells. |
| title_sort | kuwanon v inhibits proliferation promotes cell survival and increases neurogenesis of neural stem cells |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0118188&type=printable |
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