Academic Journal
Pharmacological inhibition of MALT1 protease activity protects mice in a mouse model of multiple sclerosis
| العنوان: | Pharmacological inhibition of MALT1 protease activity protects mice in a mouse model of multiple sclerosis |
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| المؤلفون: | Mc Guire, Conor, Elton, Lynn, Wieghofer, Peter, Staal, Jens, Voet, Sofie, Demeyer, Annelies, Nagel, Daniel, Krappmann, Daniel, Prinz, Marco, Beyaert, Rudi, van Loo, Geert |
| المصدر: | JOURNAL OF NEUROINFLAMMATION ; ISSN: 1742-2094 |
| سنة النشر: | 2014 |
| المجموعة: | Ghent University Academic Bibliography |
| مصطلحات موضوعية: | Medicine and Health Sciences, A20, IMMUNE, LYMPHOMA, CLEAVAGE, ACTIVATION, ABC-DLBCL, PARACASPASE MALT1, AUTOIMMUNE-MEDIATED DEMYELINATION, NF-KAPPA-B, demyelination, mepazine, MALT1, experimental autoimmune encephalomyelitis, multiple sclerosis |
| الوصف: | Background: The paracaspase mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is crucial for lymphocyte activation through signaling to the transcription factor NF-kappa B. Besides functioning as a scaffold signaling protein, MALT1 also acts as a cysteine protease that specifically cleaves a number of substrates and contributes to specific T cell receptor-induced gene expression. Recently, small molecule inhibitors of MALT1 proteolytic activity were identified and shown to have promising anticancer properties in subtypes of B cell lymphoma. However, information on the therapeutic potential of small compound inhibitors that target MALT1 protease activity in autoimmunity is still lacking. Methods: The present study aimed to elucidate whether MALT1 protease inhibitors are also useful in the treatment of lymphocyte-mediated autoimmune pathologies such as multiple sclerosis (MS). For this, we studied the therapeutic potential of a recently identified inhibitor of MALT1 protease activity, the phenothiazine derivative mepazine, in the context of experimental autoimmune encephalomyelitis (EAE), the main animal model for MS. Results: We demonstrate that administration of mepazine prophylactically or after disease onset, can attenuate EAE. Importantly, while complete absence of MALT1 affects the differentiation of regulatory T (Treg) cells in vivo, the MALT1 protease inhibitor mepazine did not affect Treg development. Conclusions: Altogether, these data indicate that small molecule inhibitors of MALT1 not only hold great promise for the treatment of B cell lymphomas but also for autoimmune disorders such as MS. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | https://biblio.ugent.be/publication/5685214; http://hdl.handle.net/1854/LU-5685214; http://dx.doi.org/10.1186/1742-2094-11-124; https://biblio.ugent.be/publication/5685214/file/7228535 |
| DOI: | 10.1186/1742-2094-11-124 |
| الاتاحة: | https://biblio.ugent.be/publication/5685214 http://hdl.handle.net/1854/LU-5685214 https://doi.org/10.1186/1742-2094-11-124 https://biblio.ugent.be/publication/5685214/file/7228535 |
| Rights: | No license (in copyright) ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.CE5B065F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/1742-2094-11-124 |
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