Fig. 2
From: Targeting the TDP-43 low complexity domain blocks spreading of pathology in a mouse model of ALS/FTD
ACI-6677 inhibits human TDP-43 aggregation and promotes phagocytic clearance by microglia. A de novo aggregation was assessed using 2.5 μM of ACI-6677 in an assay where the TEV protease is added to cleave MBP-tagged TDP-43, initiating the aggregating process. An isotype control mAb in the presence or absence of the TEV protease provides the kinetic profiles for maximal or no aggregation, respectively; Data represent mean ± SD of 3 independent replicates. B Quantification of percent aggregation inhibition at 24 h from 2 independent experiments normalized to the isotype control without TEV protease. Data shown as mean ± SD reported using a ratio-paired t-test **p < 0.01; C Phagocytosis assay with mouse microglia of ACI-6677-TDP-43 immune complexes over 24 h; the total integrated intensity (expressed as green calibrated unit (GCU) x mm2 per image) of fluorescent pHrodo™-labeled TDP-43 (30 nM) internalized at each timepoint is reported after incubation with 30 nM of ACI-6677 or isotype control mAb. Data represents mean ± SD from three technical replicates; D Quantification of total integrated intensity at 6 h from three independent experiments normalized to the no mAbs control. Data shown as mean ± SD reported using a ratio-paired t-test *p < 0.05