Cytosolic antibody receptor TRIM21 is required for effective tau immunotherapy in mouse models
| العنوان: | Cytosolic antibody receptor TRIM21 is required for effective tau immunotherapy in mouse models |
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| المؤلفون: | Mukadam, Aamir S, Miller, Lauren VC, Smith, Annabel E, Vaysburd, Marina, Sakya, Siri A, Sanford, Sophie, Keeling, Sophie, Tuck, Benjamin J, Katsinelos, Taxiarchis, Green, Chris, Skov, Lise, Kaalund, Sanne S, Foss, Stian, Mayes, Keith, O'Connell, Kevin, Wing, Mark, Knox, Claire, Banbury, Jessica, Avezov, Edward, Rowe, James B, Goedert, Michel, Andersen, Jan Terje, James, Leo C, McEwan, William A |
| المساهمون: | Mukadam, Aamir S [0000-0002-3363-7636], Miller, Lauren VC [0000-0002-0612-494X], Smith, Annabel E [0000-0001-5837-6121], Sakya, Siri A [0000-0002-5893-6771], Sanford, Sophie [0000-0002-7712-0575], Keeling, Sophie [0000-0002-6413-2550], Tuck, Benjamin J [0000-0002-8148-542X], Katsinelos, Taxiarchis [0000-0001-6951-3216], Green, Chris [0000-0002-4690-7594], Skov, Lise [0000-0002-7142-7728], Kaalund, Sanne S [0000-0002-8975-1825], Foss, Stian [0000-0001-6527-051X], Avezov, Edward [0000-0002-2894-0585], Rowe, James B [0000-0001-7216-8679], Goedert, Michel [0000-0002-5214-7886], Andersen, Jan Terje [0000-0003-1710-1628], James, Leo C [0000-0003-2131-0334], McEwan, William A [0000-0002-4408-0407], Apollo - University of Cambridge Repository |
| المصدر: | Science. 379:1336-1341 |
| بيانات النشر: | American Association for the Advancement of Science (AAAS), 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Tripartite Motif Proteins, Mice, Disease Models, Animal, Cytosol, Multidisciplinary, Tauopathies, Ribonucleoproteins, Ubiquitin-Protein Ligases, Immunization, Passive, Animals, Antibodies, Monoclonal, tau Proteins, Receptors, Fc |
| الوصف: | Aggregates of the protein tau are proposed to drive pathogenesis in neurodegenerative diseases. Tau can be targeted by using passively transferred antibodies (Abs), but the mechanisms of Ab protection are incompletely understood. In this work, we used a variety of cell and animal model systems and showed that the cytosolic Ab receptor and E3 ligase TRIM21 (T21) could play a role in Ab protection against tau pathology. Tau-Ab complexes were internalized to the cytosol of neurons, which enabled T21 engagement and protection against seeded aggregation. Ab-mediated protection against tau pathology was lost in mice that lacked T21. Thus, the cytosolic compartment provides a site of immunotherapeutic protection, which may help in the design of Ab-based therapies in neurodegenerative disease. |
| وصف الملف: | application/pdf |
| تدمد: | 1095-9203 0036-8075 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4e8ba0a531d56b297a96ac9b07b7ee06Test https://doi.org/10.1126/science.abn1366Test |
| رقم الانضمام: | edsair.doi.dedup.....4e8ba0a531d56b297a96ac9b07b7ee06 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10959203 00368075 |
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