دورية أكاديمية
Common mouse models of tauopathy reflect early but not late human disease
| العنوان: | Common mouse models of tauopathy reflect early but not late human disease |
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| المؤلفون: | Kathrin Wenger, Arthur Viode, Christoph N. Schlaffner, Patrick van Zalm, Long Cheng, Tammy Dellovade, Xavier Langlois, Anthony Bannon, Rui Chang, Theresa R. Connors, Derek Oakley, Bernhard Renard, Juri Rappsilber, Bradley Hyman, Hanno Steen, Judith A. Steen |
| المصدر: | Molecular Neurodegeneration, Vol 18, Iss 1, Pp 1-15 (2023) |
| بيانات النشر: | BMC, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Neurology. Diseases of the nervous system LCC:Geriatrics |
| مصطلحات موضوعية: | Alzheimer’s disease, Human Tau, Post-translational modifications, Protein aggregation, Tauopathy, Mouse model, Neurology. Diseases of the nervous system, RC346-429, Geriatrics, RC952-954.6 |
| الوصف: | Abstract Background Mouse models that overexpress human mutant Tau (P301S and P301L) are commonly used in preclinical studies of Alzheimer’s Disease (AD) and while several drugs showed therapeutic effects in these mice, they were ineffective in humans. This leads to the question to which extent the murine models reflect human Tau pathology on the molecular level. Methods We isolated insoluble, aggregated Tau species from two common AD mouse models during different stages of disease and characterized the modification landscape of the aggregated Tau using targeted and untargeted mass spectrometry-based proteomics. The results were compared to human AD and to human patients that suffered from early onset dementia and that carry the P301L Tau mutation. Results Both mouse models accumulate insoluble Tau species during disease. The Tau aggregation is driven by progressive phosphorylation within the proline rich domain and the C-terminus of the protein. This is reflective of early disease stages of human AD and of the pathology of dementia patients carrying the P301L Tau mutation. However, Tau ubiquitination and acetylation, which are important to late-stage human AD are not represented in the mouse models. Conclusion AD mouse models that overexpress human Tau using risk mutations are a suitable tool for testing drug candidates that aim to intervene in the early formation of insoluble Tau species promoted by increased phosphorylation of Tau. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1750-1326 |
| العلاقة: | https://doaj.org/toc/1750-1326Test |
| DOI: | 10.1186/s13024-023-00601-y |
| الوصول الحر: | https://doaj.org/article/0d7d9b70fb6e432d8c9dc6d0e97c6577Test |
| رقم الانضمام: | edsdoj.0d7d9b70fb6e432d8c9dc6d0e97c6577 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17501326 |
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| DOI: | 10.1186/s13024-023-00601-y |