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. |