Soluble dimeric prion protein ligand activates Adgrg6 receptor but does not rescue early signs of demyelination in PrP-deficient mice
| العنوان: | Soluble dimeric prion protein ligand activates Adgrg6 receptor but does not rescue early signs of demyelination in PrP-deficient mice |
|---|---|
| المؤلفون: | Adriano Aguzzi, Gebhard F. X. Schertler, Jonas Mühle, Regina Reimann, Anna Henzi, Asvin K. K. Lakkaraju, Claudia Scheckel, Assunta Senatore, Silvia Sorce, Klaus V. Toyka |
| المساهمون: | University of Zurich, Legname, Giuseppe, Aguzzi, Adriano |
| المصدر: | PLoS ONE, Vol 15, Iss 11, p e0242137 (2020) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, Macroglial Cells, Molecular biology, Gene Expression, Nervous System, Receptors, G-Protein-Coupled, Myelin, Mice, 0302 clinical medicine, Sequencing techniques, Animal Cells, Gene expression, Medicine and Health Sciences, Enzyme-Linked Immunoassays, Receptor, 0303 health sciences, Multidisciplinary, Chemistry, Nerves, RNA sequencing, General Medicine, Animal Models, Sciatic Nerve, Recombinant Proteins, 3. Good health, Cell biology, Precipitation Techniques, medicine.anatomical_structure, Experimental Organism Systems, Peripheral nervous system, Knockout mouse, Medicine, Female, Biological Cultures, Anatomy, Cellular Types, General Agricultural and Biological Sciences, Research Article, Science, 10208 Institute of Neuropathology, 610 Medicine & health, Genetics and Molecular Biology, Glial Cells, Mouse Models, 1100 General Agricultural and Biological Sciences, Prion Proteins, Cell Line, 03 medical and health sciences, Sciatic Nerves, Model Organisms, Downregulation and upregulation, 1300 General Biochemistry, Genetics and Molecular Biology, medicine, Genetics, Immunoprecipitation, Animals, Immunoassays, 030304 developmental biology, 1000 Multidisciplinary, Activator (genetics), Skeletal muscle, Biology and Life Sciences, Cell Biology, Cell Cultures, Peptide Fragments, Immunoglobulin Fc Fragments, Research and analysis methods, Mice, Inbred C57BL, Molecular biology techniques, General Biochemistry, Immunologic Techniques, Animal Studies, 570 Life sciences, biology, Schwann Cells, Transcriptome, 030217 neurology & neurosurgery, Demyelinating Diseases |
| الوصف: | The adhesion G-protein coupled receptor Adgrg6 (formerly Gpr126) is instrumental in the development, maintenance and repair of peripheral nervous system myelin. The prion protein (PrP) is a potent activator of Adgrg6 and could be used as a potential therapeutic agent in treating peripheral demyelinating and dysmyelinating diseases. We designed a dimeric Fc-fusion protein comprising the myelinotrophic domain of PrP (FT2Fc), which activated Adgrg6 in vitro and exhibited favorable pharmacokinetic properties for in vivo treatment of peripheral neuropathies. While chronic FT2Fc treatment elicited specific transcriptomic changes in the sciatic nerves of PrP knockout mice, no amelioration of the early molecular signs demyelination was detected. Instead, RNA sequencing of sciatic nerves revealed downregulation of cytoskeletal and sarcomere genes, akin to the gene expression changes seen in myopathic skeletal muscle of PrP overexpressing mice. These results call for caution when devising myelinotrophic therapies based on PrP-derived Adgrg6 ligands. While our treatment approach was not successful, Adgrg6 remains an attractive therapeutic target to be addressed in other disease models or by using different biologically active Adgrg6 ligands. |
| وصف الملف: | journal.pone.0242137.pdf - application/pdf |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cb5f18e37731975d56f0a429ddbe362a https://doaj.org/article/95263374d6fd48b09546525b07214cbc |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....cb5f18e37731975d56f0a429ddbe362a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
|---|