Format:
Online-Ressource
Content:
Alzheimer-disease-associated beta-amyloid (A beta) is produced by sequential endoproteolysis of beta-amyloid protein precursor (beta APP): the extracellular portion is shed by cleavage in the juxtamembrane region by beta-amyloid-cleaving enzyme (BACE)/beta-secretase, after which it is cleaved by presenilin (PS)/gamma-secretase near the middle of the transmembrane domain. Thus, inhibition of either of the secretases reduces A beta generation and is a fundamental strategy for the development of drugs to prevent Alzheimer disease. However, it is not clear how small compounds reduce A beta production without inhibition of the secretases. Such compounds are expected to avoid some of the side effects of secretase inhibitors. Here, we report that destruxin E (Dx-E), a natural cyclic hexadepsipeptide, reduces A beta generation without affecting BACE or PS/gamma-secretase activity. In agreement with this, Dx-E did not inhibit Notch signaling. We found that Dx-E decreases colocalization of BACE1 and beta APP, which reduces beta-cleavage of beta APP. Therefore, the data demonstrate that Dx-E represents a novel A beta-reducing process which could have fewer side effects than secretase inhibitors. Copyright (C) 2009 S. Karger AG, Basel
In:
Datenlieferant: Open Access LMU (Ludwig-Maximilians-University Munich)
Language:
English
URN:
urn:nbn:de:bvb:19-epub-16586-9
URL:
https://doi.org/10.1159/000236902
URL:
https://nbn-resolving.org/urn:nbn:de:bvb:19-epub-16586-9
URL:
https://epub.ub.uni-muenchen.de/16586/1/10_1159_000236902.pdf
URL:
https://epub.ub.uni-muenchen.de/16586/
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