Premium
P4‐194: Presenilin‐dependent gamma‐secretase proteolysis of cytokine receptors
Author(s) -
McCarthy Justin V.,
Elzinga Baukje,
Twomey Ciara,
Harte Frances,
Powell James C.,
Wujek Piotr
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.2261
Subject(s) - presenilin , amyloid precursor protein , amyloid precursor protein secretase , biology , microbiology and biotechnology , alpha secretase , adam10 , biochemistry , metalloproteinase , alzheimer's disease , matrix metalloproteinase , medicine , disease , disintegrin
and G384A were subjected to treatment with different GSMs, and A 42 and A 38 levels were analyzed by ELISA, mass spectrometry or high-resolution SDS-urea electrophoresis. Results: After sulindac sulfide treatment, all mutant cell lines displayed a strongly reduced A 42response as compared to WT-PS1 expressing cells. Conversely, A 38 levels were increased to similar levels in the mutant cell lines. These results were confirmed with the structurally divergent GSM ibuprofen. Furthermore, mass spectrometry and SDS-urea electrophoresis did not reveal compensatory changes in levels of other secreted or intracellular A peptides. Conclusions: These data provide evidence that A 42 and A 38 can be generated independently by -secretase, and argue against a precursor-product relationship between these peptides.