Data analysis

In all experiments, means + /− SD are reported. To evaluate the significance of differences between two experimental conditions (LDH and MTT assay with HEK-293 cells as well as for evaluation of western blot analysis in USP19 transfection) statistical comparisons among groups were determined using two sample t-test assuming unequal variance. To analyse the change in intracellular and extracellular neuroserpin levels after treatment with compound 1 and BFA, the mean ratio of the normalized density data (intracellular/extracellular) was compared. Hypothesis testing was conducted on logarithmized data using a two sample t-test assuming unequal variance (Welch’s t-test). To evaluate the significance of differences of three experimental conditions (quantification of caspase 3 activation, of synaptic toxicity, for LDH assay with primary neurons and for western blot analysis of mouse hippocampal extracts) one-way analysis of variance was applied. Post-hoc analysis was subsequentially performed to determine pairwise comparison in case of prior significance. For this, Tukey’s ‘Honest Significant Difference’ method was used correcting for multiple testing. n and p values are found in figure legends and in the Results section. Statistical significance was set at *p ≤ 0.05, **p ≤ 0.01 and ***p ≤ 0.001. The following statistical software were used: GraphPad Prism version 5.0 (GraphPad Software), Excel (Microsoft-Office), R statistical computing language (version 3.6.1).