γ-Secretase Substrate Concentration Modulates the Aβ42/Aβ40 Ratio
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چکیده
منابع مشابه
Substrate docking to γ-secretase allows access of γ-secretase modulators to an allosteric site
γ-Secretase generates the peptides of Alzheimer's disease, Aβ(40) and Aβ(42), by cleaving the amyloid precursor protein within its transmembrane domain. γ-Secretase also cleaves numerous other substrates, raising concerns about γ-secretase inhibitor off-target effects. Another important class of drugs, γ-secretase modulators, alter the cleavage site of γ-secretase on amyloid precursor protein, ...
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-secretase catalyzes the intramembrane cleavage of amyloid precursor protein (APP) and Notch after their extracellular domains are shed by site-specific proteolysis. Nicastrin is an essential glycoprotein component of the -secretase complex but has no known function. We now show that the ectodomain of nicastrin binds the new amino terminus that is generated upon proteolysis of the extracellular...
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cDNAs and Antibodies Human cDNAs were used in this study unless indicated otherwise. Wild-type and mutant Nct-His, PS1, APH-1aL-His, HA-PEN-2, Flag-PEN-2, C99-Flag, nFlag-C99, N100-Flag/His, and His-Syt1 cDNAs were cloned into pFASTBac and baculoviruses were generated using the Bac-to-Bac Baculovirus Expression System (Invitrogen). pFASTBac/C99-Flag encodes C-terminally Flag-tagged C99 with a M...
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Podoplanin (PDPN) is a mucin-like transmembrane glycoprotein that plays an important role in development and cancer. Here, we provide evidence that the intracellular domain (ICD) of podoplanin is released into the cytosol following a sequential proteolytic processing by a metalloprotease and γ-secretase. Western blotting and cell fractionation studies revealed that HEK293T and MDCK cells transf...
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γ-Secretase catalyzes the final cleavage of the amyloid precursor protein (APP), resulting in the production of amyloid-β (Aβ) peptides with different carboxyl termini. Presenilin (PSEN) and amyloid precursor protein (APP) mutations linked to early onset familial Alzheimer's disease modify the profile of Aβ isoforms generated, by altering both the initial γ-secretase cleavage site and subsequen...
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ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 2007
ISSN: 0021-9258
DOI: 10.1074/jbc.m704601200