Regulation of UPR genes expression, bioenergetics, and cell viability of thapsigargin-treated a WT Tau and b P301L cells compared to thapsigargin-treated Mock cells. a, b Fold-change regulation of UPR genes of Th-treated a WT Tau cells and b P301L cells compared to Th-treated Mock cells. (c, d) Fold-change regulation of significantly up-regulated UPR genes in Th-treated WT Tau and P301L cells compared to Th-treated Mock cells of two selected functional groups. Values were calculated based on a Student’s t test of the replicate values for each gene (n = 3 replicates of 3 independent experiments), and P < 0.05 were considered significant. e, f ATP level, MMP level and LDH level of e Th-treated WT Tau cells and f Th-treated P301L cells compared to Th-treated Mock cells. Values represent the mean ± SEM (n = 18–60 replicates of 3–5 independent experiments) and were normalized to Th-treated Mock cells (= 100%). Statistical analysis was performed using One-Way ANOVA followed by Turkey’s Multiple Comparison Test: *P < 0.05 and ***P < 0.001. ATP adenosine triphosphate (major energy source of cells), MMP mitochondrial membrane potential (indicator of polarization state of the mitochondrial membrane), LDH lactate dehydrogenase (released by cells into medium when integrity of cell membrane is lost—cytotoxicity detection)