Figure 3 - available via license: Creative Commons Attribution 4.0 International
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Chemical chaperone and antioxidant activities of ZN/VB compounds. (A) Thioflavin T binding assay for Tau RD (Q 244 -E 372 of Tau, NP_005901) aggregation. Top: Amino acid sequence of Tau RD -His protein, with Tau RD marked in red, ∆K280 marked in purple, in-frame-fused His 6 marked in pink, and N-terminal Met and linker (Leu and Glu) marked in blue. Bottom: Anti-aggregation assay. Tau RD protein (20 µM) was incubated with congo red, ZN-013, ZN-015, VB-030 or VB-037 (2.5-20 µM) at 37 • C for 48 h, and aggregation was monitored by measuring thioflavin T fluorescence intensity (n = 3). p values: comparisons between 0 h and 48 h ( ### : p < 0.001), wild type versus ∆K280 ( &&& : p < 0.001), or with and without compound addition (*: p < 0.05, **: p < 0.01, ***: p < 0.001) (one-way ANOVA with a post hoc Tukey test). (B) Antioxidant assays of kaempferol (as a positive control) and ZN/VB compounds (10-160 µM for DPPH free radical scavenging activity and 4-100 µM for trolox equivalent oxygen radical absorbance capacity) (n = 3).
Source publication
Misfolded aggregation of the hyperphosphorylated microtubule binding protein Tau in the brain is a pathological hallmark of Alzheimer’s disease (AD). Tau aggregation downregulates brain-derived neurotrophic factor (BDNF)/tropomycin receptor kinase B (TRKB) signaling and leads to neurotoxicity. Therefore, enhancement of BDNF/TRKB signaling could be...
Contexts in source publication
Context 1
... we examined the effects of congo red and ZN/VB compounds on Tau misfolding using His-tagged ∆K280 Tau RD proteins purified from E. coli cells [33] in thioflavin T spectroscopic assay. As shown in Figure 3A, after 48 h incubation at 37 • C, markedly increased thioflavin T fluorescence was observed with ∆K280 Tau RD protein (from 193 to 12,215 arbitrary unit (AU); p < 0.001), and the increase was significant compared to wild-type Tau RD protein (12,215 versus 3202 AU; p < 0.001). ∆K280 Tau RD aggregation was significantly reduced by congo red (20 µM), ZN-015 (10-20 µM), VB-030 (20 µM) and VB-037 (10-20 µM) (from 12,215 to 6370-3985 AU; p = 0.027−< 0.001). ...
Context 2
... DPPH and ORAC assays were performed to evaluate the antioxidant activity of ZN/VB compounds. Compared to positive-control kaempferol, only VB-037 has very weak DPPH free radical scavenging activity, while ZN-015 in 4-100 µM displayed trolox equivalent activity of 4.6-41.1 µM ( Figure 3B). In summary, the results of chemical chaperone activity of ZN-015, VB-030 and VB-037 may explain the increase of DsRed fluorescence, and the oxygen radical scavenging activity of ZN-015 may reflect the reduction of ROS in ∆K280 Tau RD -expressing cells. ...
