دورية أكاديمية
The sheddase ADAM10 is a potent modulator of prion disease
| العنوان: | The sheddase ADAM10 is a potent modulator of prion disease |
|---|---|
| المؤلفون: | Hermann C Altmeppen, Johannes Prox, Susanne Krasemann, Berta Puig, Katharina Kruszewski, Frank Dohler, Christian Bernreuther, Ana Hoxha, Luise Linsenmeier, Beata Sikorska, Pawel P Liberski, Udo Bartsch, Paul Saftig, Markus Glatzel |
| المصدر: | eLife, Vol 4 (2015) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2015. |
| سنة النشر: | 2015 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | ADAM10, neurodegeneration, prion disease, proteolytic processing, shedding, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | The prion protein (PrPC) is highly expressed in the nervous system and critically involved in prion diseases where it misfolds into pathogenic PrPSc. Moreover, it has been suggested as a receptor mediating neurotoxicity in common neurodegenerative proteinopathies such as Alzheimer's disease. PrPC is shed at the plasma membrane by the metalloprotease ADAM10, yet the impact of this on prion disease remains enigmatic. Employing conditional knockout mice, we show that depletion of ADAM10 in forebrain neurons leads to posttranslational increase of PrPC levels. Upon prion infection of these mice, clinical, biochemical, and morphological data reveal that lack of ADAM10 significantly reduces incubation times and increases PrPSc formation. In contrast, spatiotemporal analysis indicates that absence of shedding impairs spread of prion pathology. Our data support a dual role for ADAM10-mediated shedding and highlight the role of proteolytic processing in prion disease. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| Relation: | https://elifesciences.org/articles/04260; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.04260 |
| URL الوصول: | https://doaj.org/article/87cbc91b5c0144a38b87e7e8a5b595d5 |
| رقم الأكسشن: | edsdoj.87cbc91b5c0144a38b87e7e8a5b595d5 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
|---|---|
| DOI: | 10.7554/eLife.04260 |