γ-Secretase
Pharmacological Assessment of γ Secretase Activity from Rodent and Human Brain
... agents, γ- secretase inhibitors (GSIs) and γ-secretase modulators (GSMs), affect γ-secretase activity in mechanistically distinct ways ...of γ-se- ...other γ-secre- ...
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An exo-cell assay for examining real-time γ-secretase activity and inhibition
... understand γ-secretase, in vitro assays using purified exogenous recombinant substrate [10] or assays utilizing isolated membrane from systems overex- pressing substrate have been developed and reported ...
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γ Secretase inhibitor–resistant glioblastoma stem cells require RBPJ to propagate
... a γ-secretase inhibitor (GSI) or by induc- ing activation of the bone morphogenetic protein (BMP) pathway with BMP4, has shown some efficacy in preclinical studies (10, 11), bringing hope to improving brain ...
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Peripheral and central effects of γ-secretase inhibition by semagacestat in Alzheimer’s disease
... Results: Assignment to the active treatment arms was associated with reduction in plasma amyloid- β (A β ) peptides, increase in ventricular volume, decrease in cerebrospinal fluid phosphorylated tau (p-tau) and several ...
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Cholestenoic acid, an endogenous cholesterol metabolite, is a potent γ-secretase modulator
... potent γ-secretase modulator, i) its lack of ability to lower brain Aβ42 following peripheral dosing and ii) the inability to identify additional endogenous CA analogs with increased potency, suggests that ...
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NSAIDs and enantiomers of flurbiprofen target γ secretase and lower Aβ42 in vivo
... cell γ -secretase assays, indicating that these compounds directly target the γ -secretase complex that generates A β from ...targeting γ -secretase and has reduced side effects ...
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APLP1 as a cerebrospinal fluid biomarker for γ-secretase modulator treatment
... with γ-secretase inhibitors failed to reach their primary clinical endpoints; the cognitive de- cline was even worse in the treatment arm than in placebo [13, ...as γ-secretase substrates ...
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Modulation of Aβ42 in vivo by γ-secretase modulator in primates and humans
... has γ-secretase modulating activity in vivo at the dose given ...of γ-secretase modulation. These latter findings showed that γ-secretase complex can be modulated in primates in ...
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A novel Aβ isoform pattern in CSF reflects γ-secretase inhibition in Alzheimer disease
... In a previous study using ELISA measurements of CSF Aβ1-40 and Aβ1-42, the expected reduction of the peptides in response to LY450139 treatment was not found [19]. It was suggested that this lack of changes might be the ...
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ApoER2 expression increases Aβ production while decreasing Amyloid Precursor Protein (APP) endocytosis: Possible role in the partitioning of APP into lipid rafts and in the regulation of γ-secretase activity
... rather than the endocytosis of lipoproteins and other lig- ands [25]. It is currently known that ApoER2 participates in the reelin signaling pathway during neuronal develop- ment [42-44], and recent evidence indicates ...
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Super-resolution microscopy reveals γ-secretase at both sides of the neuronal synapse
... of γ-secretase was studied by immunohistochemistry and STED microscopy, using synaptophysin or synaptobrevin as presynaptic marker and PSD95 as postsynaptic ...marker. γ-Secretase was labeled ...
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Sortilin, SorCS1b, and SorLA Vps10p sorting receptors, are novel γ-secretase substrates
... other γ-secretase substrates and evidence for ectodomain shedding [42] (Figure 1a), we hypothesized that the mammalian Vps10p containing family of proteins might be γ-secretase sub- ...
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The cytotoxicity of γ secretase inhibitor I to breast cancer cells is mediated by proteasome inhibition, not by γ secretase inhibition
... It should be pointed out that although the latest study by Rasul and colleagues found that Z-LLNle-CHO has proteasome inhibitory function at concentrations that showed dose- dependent cytotoxicity [27], the authors did ...
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QSAR STUDIES & DESIGNING OF POTENT HETEROCYCLIC COMPOUNDS AS γ SECRETASE INHIBITORS
... For designing of potent molecule as γ-secretase inhibitor the suggestion provided are same i.e. increasing NH group (from 2D QSAR) and steric properties (from 3D QSAR). On this basis we have design 18 ...
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Papillomavirus Infection Requires γ Secretase
... ␥ secretase are typically precut with a proprotein convertase at a position less than 30 residues from the transmembrane domain to reveal a free amine to facilitate NCT recognition ...␥ secretase are within ...
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Vesicular Trafficking of Incoming Human Papillomavirus 16 to the Golgi Apparatus and Endoplasmic Reticulum Requires γ Secretase Activity
... To determine if the L2 FLAG tag was constitutively exposed in intact capsids, we tested if HPV16.L2F was neutralized by anti- FLAG antibody. HPV16 PsV and HPV16.L2F were incubated with monoclonal anti-FLAG prior to ...
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The amyloid-beta forming tripeptide cleavage mechanism of γ-secretase
... We show that the majority of FAD mutants within the TMD of APP primarily increase the Ab42/40 ratio by changing e cleavage, favoring the Ab48 fi 42 pathway. This is mostly in agreement with pre- vious studies ...
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Presenilins and the γ-secretase: still a complex problem
... The possibility that C99 needs to partially slip out of the membrane may also explain why g-secretase cleaves APP at multiple sites. While the commonly held view is that g-secretase cleavage involves the ...
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Biological function of Presenilin and its role in AD pathogenesis
... [67]. γ-secretase is a multi-unit enzymatic complex, including presenilin NTF/CTF heterodimer, nicastrin, Aph-1 and Pen-2 ...with γ-secretase in vivo and in ...duced γ-secretase ...
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The impact of neuronal Notch-1/JNK pathway on intracerebral hemorrhage-induced neuronal injury of rat model
... To determine a role of Notch-1 in the phosphorylation of JNK, blocking Notch signaling activation by a γ-secretase inhibitor, DAPT was applied, and then relevant proteins including p-JNK and active caspase ...
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