VBP15, a novel anti‐inflammatory and membrane‐stabilizer, improves muscular dystrophy without side effects
| العنوان: | VBP15, a novel anti‐inflammatory and membrane‐stabilizer, improves muscular dystrophy without side effects |
|---|---|
| المؤلفون: | Christopher R. Heier, Edward M. Connor, Kathleen Tatem, Kanneboyina Nagaraju, Sarah Jordan, Luana Scheffer, Qing Yu, Tony Huynh, Michael E. Calhoun, Jack H. Van der Meulen, Olga Rodriguez, John M. McCall, Heather Gordish-Dressman, Erica K.M. Reeves, Sherry Dadgar, Eric P. Hoffman, Chris Albanese, Jesse M. Damsker, Arpana Sali, Brittany K. Miller, James L Quinn, Aditi Phadke, Blythe C. Dillingham, Jyoti K. Jaiswal |
| المصدر: | EMBO Molecular Medicine |
| بيانات النشر: | EMBO, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Transcription, Genetic, muscle, T-Lymphocytes, Duchenne muscular dystrophy, Anti-Inflammatory Agents, Pharmacology, Muscular Dystrophies, Myoblasts, Mice, 0302 clinical medicine, Glucocorticoid receptor, Protein Interaction Maps, Muscular dystrophy, Pregnadienediols, Research Articles, anti-inflammatory, 0303 health sciences, biology, NF-kappa B, 3. Good health, Phenotype, medicine.anatomical_structure, dystrophy, Prednisolone, Molecular Medicine, medicine.symptom, Dystrophin, mdx, Immunosuppressive Agents, Signal Transduction, medicine.drug, Inflammation, Cell Line, Necrosis, 03 medical and health sciences, Receptors, Glucocorticoid, medicine, Animals, 030304 developmental biology, Lasers, Cell Membrane, Dystrophy, Skeletal muscle, medicine.disease, Immunology, Mice, Inbred mdx, biology.protein, membrane injury, 030217 neurology & neurosurgery |
| الوصف: | Absence of dystrophin makes skeletal muscle more susceptible to injury, resulting in breaches of the plasma membrane and chronic inflammation in Duchenne muscular dystrophy (DMD). Current management by glucocorticoids has unclear molecular benefits and harsh side effects. It is uncertain whether therapies that avoid hormonal stunting of growth and development, and/or immunosuppression, would be more or less beneficial. Here, we discover an oral drug with mechanisms that provide efficacy through anti-inflammatory signaling and membrane-stabilizing pathways, independent of hormonal or immunosuppressive effects. We find VBP15 protects and promotes efficient repair of skeletal muscle cells upon laser injury, in opposition to prednisolone. Potent inhibition of NF-κB is mediated through protein interactions of the glucocorticoid receptor, however VBP15 shows significantly reduced hormonal receptor transcriptional activity. The translation of these drug mechanisms into DMD model mice improves muscle strength, live-imaging and pathology through both preventive and post-onset intervention regimens. These data demonstrate successful improvement of dystrophy independent of hormonal, growth, or immunosuppressive effects, indicating VBP15 merits clinical investigation for DMD and would benefit other chronic inflammatory diseases. |
| تدمد: | 1757-4684 1757-4676 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::02c13bf4cb0c72ae72ab36bacfec805cTest https://doi.org/10.1002/emmm.201302621Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....02c13bf4cb0c72ae72ab36bacfec805c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17574684 17574676 |
|---|