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Dimethylarginine dimethylaminohydrolase 1 as a novel regulator of oligodendrocyte differentiation in the central nervous system remyelination
Author(s) -
Uyeda Akiko,
Quan Lili,
Kato Yuki,
Muramatsu Nagaaki,
Tanabe Shogo,
Sakai Kazuhisa,
Ichinohe Noritaka,
Kawahara Yukio,
Suzuki Tatsunori,
Muramatsu Rieko
Publication year - 2021
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.24060
Subject(s) - remyelination , oligodendrocyte , biology , neuroscience , experimental autoimmune encephalomyelitis , myelin , regulator , multiple sclerosis , microbiology and biotechnology , central nervous system , immunology , genetics , gene
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.