Should we measure ambivalence to change?

Détails

ID Serval
serval:BIB_15B9D36006AC
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Lettre (letter): communication adressée à l'éditeur.
Collection
Publications
Institution
Titre
Should we measure ambivalence to change?
Périodique
Addiction (Abingdon, England)
Auteur(s)
Daeppen J.B.
ISSN
1360-0443 (Electronic)
ISSN-L
0965-2140
Statut éditorial
Publié
Date de publication
11/2016
Peer-reviewed
Oui
Volume
111
Numéro
11
Pages
1908-1909
Langue
anglais
Notes
Publication types: ARTICLE

Résumé
Notch is a membrane inserted protein activated by the membrane-inserted γ-secretase proteolytic complex. The Notch pathway is a potential therapeutic target for the treatment of renal diseases but also controls the function of other cells, requiring cell-targeting of Notch antagonists. Toward selective targeting, we have developed the γ-secretase inhibitor-based prodrugs 13a and 15a as substrates for γ-glutamyltranspeptidase (γ-GT) and/or γ-glutamylcyclotransferase (γ-GCT) as well as aminopeptidase A (APA), which are overexpressed in renal diseases, and have evaluated them in experimental in vitro and in vivo models. In nondiseased mice, the cleavage product from Ac-γ-Glu-γ-secretase inhibitor prodrug 13a (γ-GT-targeting and γ-GCT-targeting) but not from Ac-α-Glu-γ-secretase inhibitor prodrug 15a (APA-targeting) accumulated in kidneys when compared to blood and liver. Potential nephroprotective effects of the γ-secretase inhibitor targeted prodrugs were investigated in vivo in a mouse model of acute kidney injury, demonstrating that the expression of Notch1 and cleaved Notch1 could be selectively down-regulated upon treatment with the Ac-γ-Glu-γ-secretase-inhibitor 13a.
Pubmed
Open Access
Oui
Création de la notice
16/02/2016 18:46
Dernière modification de la notice
20/08/2019 13:44
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