Extended Data Fig. 8.

A. Representative immunoblot of mutant APP in media and lysates collected from CHO^7PA2 cells treated with IXA1 or IXA4 (10 μM) in the presence or absence of 4μ8c (64 μM). Cells were treated for 18 hrs, media was then replaced and conditioned in the presence of treatments for 24 hrs before harvesting.

B. Representative immunoblot of mutant APP in media and lysates collected from CHO^7PA2 cells treated with IXA4 or IXA6 (10 μM) in the presence or absence of MG132 (10 μM) for 18hrs.

C. Quantification of immunoblots represented in panel B of relative APP signal in lysates or conditioned media from CHO^7PA2 cells treated with IRE1/XBP1s activators IXA4 or IXA6 (10 μM) in the presence or absence of MG132 (10 μM) for 18hrs. Error bars represent SE for n=4 replicates. Statistics calculated from one-tailed Student’s t-test. *p<0.05, **p<0.01, ***p<0.001.

D. Representative autoradiogram showing the [³⁵S] metabolic labeling of mutant APP in CHO^7PA2 cells treated with IXA6 (10 μM) for 16 hrs prior to 30 min labeling. Media and lysates were collected at 0, 1, or 2 hrs and [³⁵S]-labeled mutant APP was isolated by immunopurification. The experimental protocol is shown above. Fraction remaining was calculated as described in Fig. 5D and fraction secretion was calculated as in Fig. 5E. Error bars represent SD for n = 3 replicates. P-values were calculated from one-tailed Student’s t-test. *p<0.05.