The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.
A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain.
B De Strooper; W Annaert; P Cupers; P Saftig; K Craessaerts; J S Mumm; E H Schroeter; V Schrijvers; M S Wolfe; W J Ray; et al. (Profiled Author: Goate, Alison M)
Neuronal Cell Biology and Gene Transfer Laboratory, Flanders Institute for Biotechnology (VIB4), Center for Human Genetics, KU Leuven, Belgium. Bart.Destrooper@med.kuleuven.ac.be
Signalling through the receptor protein Notch, which is involved in crucial cell-fate decisions during development, requires ligand-induced cleavage of Notch. This cleavage occurs within the predicted transmembrane domain, releasing the Notch intracellular domain (NICD), and is reminiscent of gamma-secretase-mediated cleavage of beta-amyloid precursor protein (APP), a critical event in the pathogenesis of Alzheimer's disease. A deficiency in presenilin-1 (PS1) inhibits processing of APP by gamma-secretase in mammalian cells, and genetic interactions between Notch and PS1 homologues in Caenorhabditis elegans indicate that the presenilins may modulate the Notch signalling pathway. Here we report that, in mammalian cells, PS1 deficiency also reduces the proteolytic release of NICD from a truncated Notch construct, thus identifying the specific biochemical step of the Notch signalling pathway that is affected by PS1. Moreover, several gamma-secretase inhibitors block this same step in Notch processing, indicating that related protease activities are responsible for cleavage within the predicted transmembrane domains of Notch and APP. Thus the targeting of gamma-secretase for the treatment of Alzheimer's disease may risk toxicity caused by reduced Notch signalling.
This section shows information related to the publication - computed using the fingerprint of the publication - including related publications, related experts and related grants with fingerprints representing significant amounts of overlap between their fingerprint and this publication. The red dots indicate whether those experts or terms appear within the publication, thereby showing potential and actual connections.
Golde, Todd E
10 April 2000 - 30 April 2009
NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
Total Funding: $ 2,532,291
Gandy, Samuel E
1 September 2005 - 30 June 2008
NATIONAL INSTITUTE ON AGING
Total Funding: $ 898,167
TANZI, RUDOLPH EMILE
30 September 2012 - 31 August 2017
NATIONAL INSTITUTE ON AGING
Total Funding: $ 345,936
C Haass; D J SelkoeNature 1998;391(6665):339-40.
T Tomita; T Y Chang; T Kodama; T IwatsuboNeuroreport 1998;9(5):911-3.
Tong Li; Guojun Ma; Huaibin Cai; Donald L Price; Philip C WongThe Journal of neuroscience : the official journal of the Society for Neuroscience 2003;23(8):3272-7.
Appears in this Publication
Author of this Publication