Dimethylarginine dimethylaminohydrolase 1 as a novel regulator of oligodendrocyte differentiation in the central nervous system remyelination
| Autor: | Tatsunori Suzuki, Rieko Muramatsu, Yuki Kato, Lili Quan, Yukio Kawahara, Noritaka Ichinohe, Shogo Tanabe, Akiko Uyeda, Kazuhisa Sakai, Nagaaki Muramatsu |
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| Rok vydání: | 2021 |
| Předmět: |
Central Nervous System
Central nervous system Regulator Biology Amidohydrolases Cuprizone Mice Cellular and Molecular Neuroscience medicine Animals Gene silencing Remyelination Myelin Sheath Experimental autoimmune encephalomyelitis Oligodendrocyte differentiation Cell Differentiation medicine.disease Oligodendrocyte Cell biology Myelin basic protein Mice Inbred C57BL Oligodendroglia medicine.anatomical_structure Neurology biology.protein |
| Zdroj: | Glia. 69:2591-2604 |
| ISSN: | 1098-1136 0894-1491 |
| DOI: | 10.1002/glia.24060 |
| Popis: | Remyelination is a regenerative process that restores the lost neurological function and partially depends on oligodendrocyte differentiation. Differentiation of oligodendrocytes spontaneously occurs after demyelination, depending on the cell intrinsic mechanisms. By combining a loss-of-function genomic screen with a web-resource-based candidate gene identification approach, we identified that dimethylarginine dimethylaminohydrolase 1 (DDAH1) is a novel regulator of oligodendrocyte differentiation. Silencing DDAH1 in oligodendrocytes prevented the expression of myelin basic protein in mouse oligodendrocyte culture with the change in expression of genes annotated with oligodendrocyte development. DDAH1 inhibition attenuated spontaneous remyelination in a cuprizone-induced demyelinated mouse model. Conversely, increased DDAH1 expression enhanced remyelination capacity in experimental autoimmune encephalomyelitis. These results provide a novel therapeutic option for demyelinating diseases by modulating DDAH1 activity. |
| Databáze: | OpenAIRE |
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