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Mannioui, Abdelkrim; Vauzanges, Quentin; Fini, Jean Baptiste; Henriet, Esther; Sekizar, Somya; Azoyan, Loris; Thomas, Jean Léon; Pasquier, David Du; Giovannangeli, Carine; Demeneix, Barbara; Lubetzki, Catherine; Zalc, Bernard
Multiple sclerosis, 10/2018, Letnik: 24, Številka: 11Journal Article
Background: In multiple sclerosis, development of screening tools for remyelination-promoting molecules is timely. Objective: A Xenopus transgenic line allowing conditional ablation of myelinating oligodendrocytes has been adapted for in vivo screening of remyelination-favoring molecules. Methods: In this transgenic, the green fluorescent protein reporter is fused to E. coli nitroreductase and expressed specifically in myelinating oligodendrocytes. Nitroreductase converts the innocuous pro-drug metronidazole to a cytotoxin. Spontaneous remyelination occurs after metronidazole-induced demyelinating responses. As tadpoles are transparent, these events can be monitored in vivo and quantified. At the end of metronidazole-induced demyelination, tadpoles were screened in water containing the compounds tested. After 72 h, remyelination was assayed by counting numbers of oligodendrocytes per optic nerve. Results: Among a battery of molecules tested, siponimod, a dual agonist of sphingosine-1-phosphate receptor 1 and 5, was among the most efficient favoring remyelination. Crispr/cas9 gene editing showed that the promyelinating effect of siponimod involves the sphingosine-1-phosphate receptor 5. Conclusion: This Xenopus transgenic line constitutes a simple in vivo screening platform for myelin repair therapeutics. We validated several known promyelinating compounds and demonstrated that the strong remyelinating efficacy of siponimod implicates the sphingosine-1-phosphate receptor 5.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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