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ADAM30 Downregulates APP-Linked Defects Through Cathepsin D Activation in Alzheimer's Disease

التفاصيل البيبلوغرافية
العنوان: ADAM30 Downregulates APP-Linked Defects Through Cathepsin D Activation in Alzheimer's Disease
المؤلفون: Florent Letronne, Geoffroy Laumet, Anne-Marie Ayral, Julien Chapuis, Florie Demiautte, Mathias Laga, Michel E. Vandenberghe, Nicolas Malmanche, Florence Leroux, Fanny Eysert, Yoann Sottejeau, Linda Chami, Amandine Flaig, Charlotte Bauer, Pierre Dourlen, Marie Lesaffre, Charlotte Delay, Ludovic Huot, Julie Dumont, Elisabeth Werkmeister, Franck Lafont, Tiago Mendes, Franck Hansmannel, Bart Dermaut, Benoit Deprez, Anne-Sophie Hérard, Marc Dhenain, Nicolas Souedet, Florence Pasquier, David Tulasne, Claudine Berr, Jean-Jacques Hauw, Yves Lemoine, Philippe Amouyel, David Mann, Rebecca Déprez, Frédéric Checler, David Hot, Thierry Delzescaux, Kris Gevaert, Jean-Charles Lambert
المصدر: EBioMedicine, Vol 9, Iss C, Pp 278-292 (2016)
بيانات النشر: Elsevier, 2016.
سنة النشر: 2016
المجموعة: LCC:Medicine
LCC:Medicine (General)
مصطلحات موضوعية: Alzheimer, APP, ADAM30, Amyloid, Metabolism, LTP, Medicine, Medicine (General), R5-920
الوصف: Although several ADAMs (A disintegrin-like and metalloproteases) have been shown to contribute to the amyloid precursor protein (APP) metabolism, the full spectrum of metalloproteases involved in this metabolism remains to be established. Transcriptomic analyses centred on metalloprotease genes unraveled a 50% decrease in ADAM30 expression that inversely correlates with amyloid load in Alzheimer's disease brains. Accordingly, in vitro down- or up-regulation of ADAM30 expression triggered an increase/decrease in Aβ peptides levels whereas expression of a biologically inactive ADAM30 (ADAM30mut) did not affect Aβ secretion. Proteomics/cell-based experiments showed that ADAM30-dependent regulation of APP metabolism required both cathepsin D (CTSD) activation and APP sorting to lysosomes. Accordingly, in Alzheimer-like transgenic mice, neuronal ADAM30 over-expression lowered Aβ42 secretion in neuron primary cultures, soluble Aβ42 and amyloid plaque load levels in the brain and concomitantly enhanced CTSD activity and finally rescued long term potentiation alterations. Our data thus indicate that lowering ADAM30 expression may favor Aβ production, thereby contributing to Alzheimer's disease development.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2352-3964
Relation: http://www.sciencedirect.com/science/article/pii/S2352396416302468; https://doaj.org/toc/2352-3964
DOI: 10.1016/j.ebiom.2016.06.002
URL الوصول: https://doaj.org/article/b6a220c6a95c4d56a4492c3f25a412a8
رقم الأكسشن: edsdoj.b6a220c6a95c4d56a4492c3f25a412a8
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:23523964
DOI:10.1016/j.ebiom.2016.06.002