[PDF] Top 20 Presenilins and the γ-secretase: still a complex problem

... While much progress has been made in elucidating the structure and metabolism of PS, its binding partners and the relationship between FAD mutations and Ab produc- tion, many questions remain unanswered. Experiments ... See full document

... Furthermore, γ-secretase inhibi- tor does not influence the effect of presenilins on synaptic scaling, suggesting that this function is independent of γ-secretase in AD ...of ... See full document

... independent γ- secretase complexes in cell membranes, and PS2 does not co-precipitate with PS1 fragments in membrane ex- tracts ...As presenilins are proteins with large numbers of hydrophobic ... See full document

... the γ-secretase complex, releasing an intra- cellular domain, Notch1 IC ...of γ-secretase were developed first and are the most studied in terms of clinical trials for both Alzheimer’s ... See full document

... is still a matter of ...mitochondrial γ-secretase sec- tion of this review) and direct import either from ER or from ...TOM40 complex was shown to transport Aβ across the outer mitochondrial ... See full document

... While most studies have shown that canonical Notch signaling activates tar- get genes through the DNA-binding RBPJ protein complex, Rbpj knockout mice do not have the same phenotype as Notch knockout mice (34). ... See full document

... a complex mental disorder that causes a range of different psychological symptoms, including positive symptoms, negative symptoms, and cognitive dysfunction (Tandon et ... See full document

... 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 ... See full document

... 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 ... See full document

... 94 Notch signaling is important for intestinal tumor initiation, but not for tumor progression (Fre et al., 2009). A 20-fold increase in the number of adenomas was observed in mice with Apc mutation combined with Notch ... See full document

... 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 ... See full document

... Inhibition of the two isoforms of cyclooxygenase (COX1 and COX2) is the primary pharmacological action of NSAIDs that results in their anti-inflamma- tory properties (38). Some NSAIDs activate the perox- isome ... See full document

... a γ-secretase inhibitor (IL- aldehyde) for 30 hours and sucrose gradient fractions 4, 5 were combined and analyzed for generation of the smaller SorV5 ...of γ-secretase inhibi- tors, LY411575, ... See full document

... as γ- secretase-mediated cleavage of ephrin-B (data not ...undergoes γ- secretase-dependent intramembrane cleavage independ- ently of its cytoplasmic C terminus, that contains a PDZ domain ... See full document

... 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 ... See full document

... TSC1/2 complex by its phosphorylation and in this way activate mTORC1, which negatively regulates autophagy through inhibitory phosphorylation of Ulk1 and Ulk2 ...TSC1/2 complex switches autophagy off by ... See full document

... inhibits γ-secretase, a key enzyme for generation of amyloid β (Aβ), the peptide deposited in plaques in Alzheimer disease ...during γ-secretase inhibitor treatment, and thus may serve as ... See full document

... with γ-secretase inhibitors of the Notch pathway, a key regulator of intestinal progenitor cells, colon cancer, and inflam- mation, demonstrated enhanced intestinal goblet cell differentiation as compared ... See full document

... 1996). Presenilins seem to be involved in signal transduction (possibly in a complex together with APP), protein trafficking, and/or in proper chromosome segregation during mitosis (Xia et ...that ... See full document

... 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 ... See full document