Selective inhibitors of the PSEN1-gamma-secretase complex. [PDF]
J Biol Chem, 2023 Clinical development of γ-secretases, a family of intramembrane cleaving proteases, as therapeutic targets for a variety of disorders including cancer and Alzheimer's disease was aborted because of serious mechanism-based side effects in the phase III trials of unselective inhibitors.
Serneels L +12 more
europepmc +7 more sources
Gamma Secretase Inhibitors in Cancer: A Current Perspective on Clinical Performance [PDF]
Oncologist, 2021 Tyler R Mccaw +2 more
exaly +2 more sources
Conformational Models of APP Processing by Gamma Secretase Based on Analysis of Pathogenic Mutations [PDF]
International Journal of Molecular Sciences, 2021 Ilya Bezprozvanny, Bezprozvanny Ilya
exaly +2 more sources
Synaptic and endosomal localization of active gamma-secretase in rat brain. [PDF]
PLoS ONE, 2010 A key player in the development of Alzheimer's disease (AD) is the gamma-secretase complex consisting of at least four components: presenilin, nicastrin, Aph-1 and Pen-2.
Susanne Frykman +7 more
doaj +1 more source
Gender- and age-dependent gamma-secretase activity in mouse brain and its implication in sporadic Alzheimer disease. [PDF]
PLoS ONE, 2009 Alzheimer disease (AD) is an age-related disorder. Aging and female gender are two important risk factors associated with sporadic AD. However, the mechanism by which aging and gender contribute to the pathogenesis of sporadic AD is unclear.
Lisa Placanica, Lei Zhu, Yue-Ming Li
doaj +1 more source
Gamma-secretase: from pathogenesis to therapeutics [PDF]
Molecular Neurodegeneration, 2012 Background Presenilin (PS) is the catalytic subunit of g-secretase and mutations in this protein cause familial Alzheimer’s Disease (FAD). Moreover, g-secretase has emerged as an appealing drug target for Alzheimer’s disease (AD) and cancer due to its central role in the generation of Ab peptides and the regulation of Notch signaling.
Li Yueming
doaj +2 more sources
Proteomic profiling of gamma-secretase substrates and mapping of substrate requirements. [PDF]
PLoS Biology, 2008 The presenilin/gamma-secretase complex, an unusual intramembrane aspartyl protease, plays an essential role in cellular signaling and membrane protein turnover.
Matthew L Hemming +3 more
doaj +1 more source
gamma-Secretase dependent production of intracellular domains is reduced in adult compared to embryonic rat brain membranes. [PDF]
PLoS ONE, 2010 BACKGROUND: gamma-Secretase is an intramembrane aspartyl protease whose cleavage of the amyloid precursor protein (APP) generates the amyloid beta-peptide (Abeta) and the APP intracellular domain.
Jenny Frånberg +4 more
doaj +1 more source
Allosteric modulation of PS1/gamma-secretase conformation correlates with amyloid beta(42/40) ratio. [PDF]
PLoS ONE, 2009 Presenilin 1(PS1) is the catalytic subunit of gamma-secretase, the enzyme responsible for the Abeta C-terminal cleavage site, which results in the production of Abeta peptides of various lengths.
Kengo Uemura +9 more
doaj +1 more source
Role of cholesterol in substrate recognition by $$\gamma$$ γ -secretase
Scientific Reports, 2021 $$\gamma$$ γ -Secretase is an enzyme known to cleave multiple substrates within their transmembrane domains, with the amyloid precursor protein of Alzheimer’s Disease among the most prominent examples.
Łukasz Nierzwicki +3 more
doaj +1 more source