Fig. 9.

CTSB inhibition promotes pSyn-S129 accumulation in patient-derived midbrain organoids. A Representative immunofluorescent images of Map2 and pSyn-S129 in 5-month old SNCA-triplication (3xSNCA) and isogenic SNCA-KO midbrain organoids treated with vehicle (DMSO) or 1 μM CA074me for 60 days. Large images depict representative whole-organoids and high-magnification images depict individual Map2-positive cells. B Quantification of the pSyn-S129 positive area of the organoid relative to the total organoid size. C Quantification of the Map2-positive area relative to organoid size. D Quantification of pSyn-S129- and Map2 double-positive area in 3 × SNCA organoids. E Quantification of the percentage of cells positive for both Map2 and pSyn-S129 in 3 × SNCA organoids. Bonferroni-corrected t-tests, * p < 0.05