دورية أكاديمية
Teriflunomide Promotes Oligodendroglial 8,9-Unsaturated Sterol Accumulation and CNS Remyelination
| العنوان: | Teriflunomide Promotes Oligodendroglial 8,9-Unsaturated Sterol Accumulation and CNS Remyelination |
|---|---|
| المؤلفون: | Martin, Elodie, Aigrot, Marie-Stephane, Lamari, Foudil, Bachelin, Corinne, Lubetzki, Catherine, Nait Oumesmar, Brahim, Zalc, Bernard, Stankoff, Bruno |
| المساهمون: | Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | ISSN: 2332-7812 ; Neurology Neuroimmunology & Neuroinflammation ; https://hal.sorbonne-universite.fr/hal-03561653Test ; Neurology Neuroimmunology & Neuroinflammation, 2021, 8 (6), pp.e1091. ⟨10.1212/nxi.0000000000001091⟩. |
| بيانات النشر: | HAL CCSD American Academy of neurology |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | MESH: Animals, Newborn, MESH: Larva, MESH: Mice, Inbred C57BL, Transgenic, MESH: Nitriles, MESH: Oligodendrocyte Precursor Cells, MESH: Oligodendroglia, MESH: Remyelination, MESH: Toluidines, MESH: Xenopus laevis, MESH: Cells, Cultured, MESH: Central Nervous System Diseases, MESH: Cholesterol, MESH: Crotonates, MESH: Demyelinating Diseases, MESH: Disease Models, Animal, MESH: Hydroxybutyrates, MESH: Immunosuppressive Agents, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] |
| الوصف: | International audience ; Background and Objectives To test whether low concentrations of teriflunomide (TF) could promote remyelination, we investigate the effect of TF on oligodendrocyte in culture and on remyelination in vivo in 2 demyelinating models.Methods The effect of TF on oligodendrocyte precursor cell (OPC) proliferation and differentiation was assessed in vitro in glial cultures derived from neonatal mice and confirmed on fluorescence-activated cell sorting–sorted adult OPCs. The levels of the 8,9-unsaturated sterols lanosterol and zymosterol were quantified in TF- and sham-treated cultures. In vivo, TF was administered orally, and remyelination was assessed both in myelin basic protein–GFP-nitroreductase (Mbp:GFP-NTR) transgenic Xenopus laevis demyelinated by metronidazole and in adult mice demyelinated by lysolecithin.Results In cultures, low concentrations of TF down to 10 nM decreased OPC proliferation and increased their differentiation, an effect that was also detected on adult OPCs. Oligodendrocyte differentiation induced by TF was abrogated by the oxidosqualene cyclase inhibitor Ro 48-8071 and was mediated by the accumulation of zymosterol. In the demyelinated tadpole, TF enhanced the regeneration of mature oligodendrocytes up to 2.5-fold. In the mouse demyelinated spinal cord, TF promoted the differentiation of newly generated oligodendrocytes by a factor of 1.7-fold and significantly increased remyelination.Discussion TF enhances zymosterol accumulation in oligodendrocytes and CNS myelin repair, a beneficial off-target effect that should be investigated in patients with multiple sclerosis. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/34642237; hal-03561653; https://hal.sorbonne-universite.fr/hal-03561653Test; https://hal.sorbonne-universite.fr/hal-03561653/documentTest; https://hal.sorbonne-universite.fr/hal-03561653/file/e1091.full.pdfTest; PUBMED: 34642237; PUBMEDCENTRAL: PMC8515201 |
| DOI: | 10.1212/nxi.0000000000001091 |
| الإتاحة: | https://doi.org/10.1212/nxi.0000000000001091Test https://hal.sorbonne-universite.fr/hal-03561653Test https://hal.sorbonne-universite.fr/hal-03561653/documentTest https://hal.sorbonne-universite.fr/hal-03561653/file/e1091.full.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.D0AA395A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1212/nxi.0000000000001091 |
|---|