Figure 4.
Cathepsin B protein expression is decreased in iPSC derived neurons from GBA p.N370S carriers. Forebrain neurons differentiated from patient iPSCs with GBA mutations have decreased cathepsin B protein expression. (A) Representative western blot showing protein levels of active cathepsin B (CTSB, 24 and 29 kDa) and neuron associated β-III tubulin (50 kDa) in forebrain neurons differentiated from individuals with and without Parkinson’s disease-associated GBA variants (n = 2 lines from each genotype; all lines tested are heterozygous at rs1293298). (B) Quantification of the mean active cathepsin B protein levels relative to β-III tubulin shows a significant decrease (*P < 0.05; unpaired t-test, n = 2 lines of each genotype with three technical replicates each) in cathepsin B levels in forebrain neurons differentiated from GBA p.N370S carriers compared to neurons from wild-type (WT) GBA carriers. M = protein marker; error bars represent standard error of the mean. Note that both the heavy chain and heavy plus light chain bands were quantified in this analysis.