| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
To investigate the γ-secretase independent intramembrane cleavage mechanism of amyloid β precursor protein (βAPP), we generated presenilin 1 and presenilin 2 double knockout (PSDKO) cells by CRISPR/Cas9 system. PSDKO cells were treated with various protease inhibitors and intracellular oligopeptides derived from transmembrane domain of βAPP were quantified by LC-Ms/Ms. As a result, eight tripeptides were decreased by treatment of lysosomal enzyme inhibitor chloroquine. Since these peptides were not decreased by inhibition of cathepsins, the major lysosomal proteases, it was suggested that intramembrane domain of βAPP was degraded by tripeptidyl peptidase 1, which releases tripeptides from N-termini of proteins.
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