PubMed:10400678 JSONTXT 25 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T1 0-140 DRI_Background denotes Rank-order of potencies for inhibition of the secretion of abeta40 and abeta42 suggests that both are generated by a single gamma-secretase.
T2 141-338 DRI_Background denotes The Alzheimer's disease amyloid peptide Abeta has a heterogeneous COOH terminus, as variants 40 and 42 residues long are found in neuritic plaques and are secreted constitutively by cultured cells.
T3 339-469 DRI_Outcome denotes The proteolytic activity that liberates the Abeta COOH terminus from the beta-amyloid precursor protein is called gamma-secretase.
T4 470-541 DRI_Outcome denotes It could be one protease with dual specificity or two distinct enzymes.
T5 542-782 DRI_Approach denotes By using enzyme-linked immunosorbent assays selective for Abeta40 or Abeta42, we have measured Abeta secretion by a HeLa cell line, and we have examined the dose responses for a panel of five structurally diverse gamma-secretase inhibitors.
T6 783-856 DRI_Background denotes The inhibitors lowered Abeta and p3 secretion and increased levels of the
T7 857-894 Token_Label.OUTSIDE denotes COOH-terminal 99-residue beta-amyloid
T8 895-1136 DRI_Background denotes precursor protein derivative that is the precursor for Abeta but did not alter secretion of beta-amyloid precursor protein derivatives generated by other secretases, indicating that the inhibitors blocked the gamma-secretase processing step.
T9 1137-1304 DRI_Background denotes The dose-dependent inhibition of Abeta42 was unusual, as the compounds elevated Abeta42 secretion at sub-inhibitory doses and then inhibited secretion at higher doses.
T10 1305-1515 DRI_Background denotes A compound was identified that elevated Abeta42 secretion at a low concentration without inhibiting Abeta42 or Abeta40 at high concentrations, demonstrating that these phenomena are separable pharmacologically.
T11 1516-1680 DRI_Background denotes Using either of two methods, IC50 values for inhibition of Abeta42 and Abeta40 were found to have the same rank-order and fall on a trend line with near-unit slope.
T12 1681-1805 DRI_Background denotes These results favor the hypothesis that Abeta variants ending at residue 40 or 42 are generated by a single gamma-secretase.