Title

Effects of peptides derived from BACE1 catalytic domain on APP processing.

Journal

Peptides

Volume

28

Issue

None

Pages

838-44

Date

2007-04-01

Authors

Kim TY | Jeon YJ | Yeon SW | Hwang EM

BI-3 also potentially inhibited the release of sAPPb (IC50 = 0.5 mM) and sAPPa (IC50 = 3.4 mM, Figs. 2B and 3B). BI- 4, which is short peptide of BI-3, showed no effects on sAPP secretion.

Taken together, these results show that BI-1 and BI-3 not only selectively reduce the level of APPbeta but also lead to the accumulation of APPalpha in cells with no change of full-length APP level.

Surprisingly, BI-1 treatment resulted in a drastic, dose-dependent increase in the level of intracellular APPa (Figs. 2A and 3A). BI-3 also induced the accumulation of intracellular APPa until the concentration of BI-3 was raised to 12.5 mM; however, treatment of BI-3 with 25 mM decreased the level of intracellular APPa.

Neither, BI-1 nor, BI-3, nor any of the other peptides used in this study, induced any changes of full-length APP levels. They also did not affect the level of b-actin.

These results suggest that BACE1 derived peptides do not directly inhibit BACE activities in vitro when the fluorogenic peptides are used as a substrate.

BI-1 treatment effectively reduced Ab 40 levels (IC50 = 0.06 mM) in the conditioned medium. BI-3 also inhibited Ab 40 production (IC50 = 0.2 mM), although the effective concentrations were relatively high compared to those of BI-1.

BI-1 treatment dose-dependently inhibited the release of both sAPPa and sAPPb in the conditioned medium (Figs. 2A and 3A). The 50% inhibitory concentrations (IC50) of BI-1 were about 1.5 mM for sAPPa and 0.9 mM for APPb, respectively. But BI-2, which is mainly composed of the core region BACE1 69–73, did not show the inhibitory effects

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