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First and second generation γ-secretase modulators (GSMs) modulate amyloid-β (Aβ) peptide production through different mechanisms.
Borgegard T, Juréus A, Olsson F, Rosqvist S, Sabirsh A, Rotticci D, Paulsen K, Klintenberg R, Yan H, Waldman M, Stromberg K, Nord J, Johansson J, Regner A, Parpal S, Malinowsky D, Radesater AC, Li T, Singh R, Eriksson H, Lundkvist J. Borgegard T, et al. Among authors: olsson f. J Biol Chem. 2012 Apr 6;287(15):11810-9. doi: 10.1074/jbc.M111.305227. Epub 2012 Feb 13. J Biol Chem. 2012. PMID: 22334705 Free PMC article.
The large hydrophilic loop of presenilin 1 is important for regulating gamma-secretase complex assembly and dictating the amyloid beta peptide (Abeta) Profile without affecting Notch processing.
Wanngren J, Frånberg J, Svensson AI, Laudon H, Olsson F, Winblad B, Liu F, Näslund J, Lundkvist J, Karlström H. Wanngren J, et al. Among authors: olsson f. J Biol Chem. 2010 Mar 19;285(12):8527-36. doi: 10.1074/jbc.M109.055590. Epub 2010 Jan 27. J Biol Chem. 2010. PMID: 20106965 Free PMC article.
Alzheimer's disease: presenilin 2-sparing γ-secretase inhibition is a tolerable Aβ peptide-lowering strategy.
Borgegård T, Gustavsson S, Nilsson C, Parpal S, Klintenberg R, Berg AL, Rosqvist S, Serneels L, Svensson S, Olsson F, Jin S, Yan H, Wanngren J, Jureus A, Ridderstad-Wollberg A, Wollberg P, Stockling K, Karlström H, Malmberg A, Lund J, Arvidsson PI, De Strooper B, Lendahl U, Lundkvist J. Borgegård T, et al. Among authors: olsson f. J Neurosci. 2012 Nov 28;32(48):17297-305. doi: 10.1523/JNEUROSCI.1451-12.2012. J Neurosci. 2012. PMID: 23197721 Free PMC article.
Combining an amyloid-beta (Aβ) cleaving enzyme inhibitor with a γ-secretase modulator results in an additive reduction of Aβ production.
Strömberg K, Eketjäll S, Georgievska B, Tunblad K, Eliason K, Olsson F, Radesäter AC, Klintenberg R, Arvidsson PI, von Berg S, Fälting J, Cowburn RF, Dabrowski M. Strömberg K, et al. Among authors: olsson f. FEBS J. 2015 Jan;282(1):65-73. doi: 10.1111/febs.13103. Epub 2014 Nov 7. FEBS J. 2015. PMID: 25303711 Free article.
67 results