Figure 6
From: Huntingtin cleavage product A forms in neurons and is reduced by gamma-secretase inhibitors
Inhibitors of gamma-secretase protect primary cortical HD neurons homozygous for full-length mutant huntingtin (Q140/Q140) from cell death. (a) Immunoprecipitation (IP) of mutant huntingtin from 23 DIV neurons using a monoclonal antibody against htt1-17 (mAb2B7) and probed with polyclonal anti-htt1-17 (Ab1). Arrow indicates full-length huntingtin when IP is performed with mAb2B7 while the control lanes are blank. N-terminal fragments were detected at ~100 kDa and ~80 kDa. Small blot on right is the enlargement of the second and third IP lanes with the double-sided arrow indicating a fragment ~72 kDa. The predicted mobility of cpA with 140Q ranges from ~69 kDa to ~85 kDa. (b) Graph shows MTT conversion reported as mean percentage of wild-type (WT) neurons treated with carrier (DMSO) ±SD. One-way ANOVA, p < 0.001, Bonferroni's Multiple comparison tests: * over bar indicates p < 0.001 for WT vs HD, *p < 0.001 compared to HD treated with DMSO, †p < 0.001 compared to WT treated with DMSO.