Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/69347
Title: Amyloid-precursor-protein-lowering small molecules for disease modifying therapy of Alzheimer's disease
Author: Rosenkranz, Sina Cathérine
Geissen, Markus
Härter, Kristina
Szalay, Beata
Ferrer, Isidro (Ferrer Abizanda)
Vogel, Jana
Smith, Stephen
Glatzel, Markus
Keywords: Malaltia d'Alzheimer
Membranes cel·lulars
Alzheimer's disease
Cell membranes
Issue Date: 18-Dec-2013
Publisher: Public Library of Science (PLoS)
Abstract: Alzheimer's disease (AD) is the most common form of dementia in the elderly with progressive cognitive decline and memory loss. According to the amyloid-hypothesis, AD is caused by generation and subsequent cerebral deposition of β-amyloid (Aβ). Aβ is generated through sequential cleavage of the transmembrane Amyloid-Precursor-Protein (APP) by two endoproteinases termed beta- and gamma-secretase. Increased APP-expression caused by APP gene dosage effects is a risk factor for the development of AD. Here we carried out a large scale screen for novel compounds aimed at decreasing APP-expression. For this we developed a screening system employing a cell culture model of AD. A total of 10,000 substances selected for their ability of drug-likeness and chemical diversity were tested for their potential to decrease APP-expression resulting in reduced Aβ-levels. Positive compounds were further evaluated for their effect at lower concentrations, absence of cytotoxicity and specificity. The six most promising compounds were characterized and structure function relationships were established. The novel compounds presented here provide valuable information for the development of causal therapies for AD.
Note: Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0082255
It is part of: PLoS One, 2013, vol. 8, num. 12, p. e82255
Related resource: http://dx.doi.org/10.1371/journal.pone.0082255
URI: http://hdl.handle.net/2445/69347
ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Patologia i Terapèutica Experimental)

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