| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-120 |
Sentence |
denotes |
Beta-secretase cleavage at amino acid residue 34 in the amyloid beta peptide is dependent upon gamma-secretase activity. |
| T2 |
121-240 |
Sentence |
denotes |
The amyloid beta peptides (Abeta) are the major components of the senile plaques characteristic of Alzheimer's disease. |
| T3 |
241-353 |
Sentence |
denotes |
Abeta peptides are generated from the cleavage of amyloid precursor protein (APP) by beta- and gamma-secretases. |
| T4 |
354-545 |
Sentence |
denotes |
Beta-secretase (BACE), a type-I transmembrane aspartyl protease, cleaves APP first to generate a 99-amino acid membrane-associated fragment (CT99) containing the N terminus of Abeta peptides. |
| T5 |
546-685 |
Sentence |
denotes |
Gamma-secretase, a multi-protein complex, then cleaves within the transmembrane region of CT99 to generate the C termini of Abeta peptides. |
| T6 |
686-795 |
Sentence |
denotes |
The production of Abeta peptides is, therefore, dependent on the activities of both BACE and gamma-secretase. |
| T7 |
796-897 |
Sentence |
denotes |
The cleavage of APP by BACE is believed to be a prerequisite for gamma-secretase-mediated processing. |
| T8 |
898-1110 |
Sentence |
denotes |
In the present study, we provide evidence both in vitro and in cells that BACE-mediated cleavage between amino acid residues 34 and 35 (Abeta-34 site) in the Abeta region is dependent on gamma-secretase activity. |
| T9 |
1111-1245 |
Sentence |
denotes |
In vitro, the Abeta-34 site is processed specifically by BACE1 and BACE2, but not by cathepsin D, a closely related aspartyl protease. |
| T10 |
1246-1432 |
Sentence |
denotes |
Moreover, the cleavage of the Abeta-34 site by BACE1 or BACE2 occurred only when Abeta 1- 40 peptide, a gamma-secretase cleavage product, was used as substrate, not the non-cleaved CT99. |
| T11 |
1433-1540 |
Sentence |
denotes |
In cells, overexpression of BACE1 or BACE2 dramatically increased the production of the Abeta 1-34 species. |
| T12 |
1541-1745 |
Sentence |
denotes |
More importantly, the cellular production of Abeta 1-34 species induced by overexpression of BACE1 or BACE2 was blocked by a number of known gamma-secretase inhibitors in a concentration-dependent manner. |
| T13 |
1746-1842 |
Sentence |
denotes |
These gamma-secretase inhibitors had no effect on enzymatic activity of BACE1 or BACE2 in vitro. |
| T14 |
1843-1967 |
Sentence |
denotes |
Our data thus suggest that gamma-secretase cleavage of CT99 is a prerequisite for BACE-mediated processing at Abeta-34 site. |
| T15 |
1968-2039 |
Sentence |
denotes |
Therefore, BACE and gamma-secretase activity can be mutually dependent. |
