| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-145 |
Sentence |
denotes |
The biological and pathological function of the presenilin-1 Deltaexon 9 mutation is independent of its defect to undergo proteolytic processing. |
| T2 |
146-470 |
Sentence |
denotes |
The two homologous presenilins are key factors for the generation of amyloid beta-peptide (Abeta), since Alzheimer's disease (AD)-associated mutations enhance the production of the pathologically relevant 42-amino acid Abeta (Abeta42), and a gene knockout of presenilin-1 (PS1) significantly inhibits total Abeta production. |
| T3 |
471-635 |
Sentence |
denotes |
Presenilins undergo proteolytic processing within the domain encoded by exon 9, a process that may be closely related to their biological and pathological activity. |
| T4 |
636-806 |
Sentence |
denotes |
An AD-associated mutation within the PS1 gene deletes exon 9 (PS1Deltaexon9) due to a splicing error and results in the accumulation of the uncleaved full-length protein. |
| T5 |
807-1057 |
Sentence |
denotes |
We now demonstrate the unexpected finding that the pathological activity of PS1Deltaexon9 is independent of its lack to undergo proteolytic processing, but is rather due to a point mutation (S290C) occurring at the aberrant exon 8/10 splice junction. |
| T6 |
1058-1233 |
Sentence |
denotes |
Mutagenizing the cysteine residue at position 290 to the original serine residue completely inhibits the pathological activity in regard to the elevated production of Abeta42. |
| T7 |
1234-1396 |
Sentence |
denotes |
Like PS1Deltaexon9, the resulting presenilin variant (PS1Deltaexon9 C290S) accumulates as an uncleaved protein and fully replaces endogenous presenilin fragments. |
| T8 |
1397-1562 |
Sentence |
denotes |
Moreover, PS1Deltaexon9 C290S exhibits a significantly increased biological activity in a highly sensitive in vivo assay as compared with the AD-associated mutation. |
| T9 |
1563-1756 |
Sentence |
denotes |
Therefore not only the increased Abeta42 production but also the decreased biological function of PS1Deltaexon9 is due to a point mutation and independent of the lack of proteolytic processing. |
