Figure 12. Probe ML346 (compound F1) reduces aggregation/toxicity in C. elegans models of diseases associated with polyQ expansions.

Figure 12Probe ML346 (compound F1) reduces aggregation/toxicity in C. elegans models of diseases associated with polyQ expansions

(a) C. elegans expressing YFP-tagged Q35 protein were treated with either DMSO (panel I) or PRs (panels III–V) at different concentrations (1, 5, 10 and 15 μM) for 4 days. 17-AAG was used as positive control (50 μM, panel II). Fluorescence microscopy shows proteostasis regulators that reduced Q35 aggregation (10 μM) in 6-day old animals. Panels VI–X show higher magnification images. Scale bar: 0.1 mm. (b) Proteostasis regulators suppress Q35 aggregation as shown by the quantification of fluorescent foci in 6-day old animals, relative to DMSO. (c) Rescue from polyQ-associated toxicity was determined by comparing the motility of Q35 animals treated with either DMSO alone or the candidate PRs compounds (10 μM) to that of WT animals in DMSO. Standard error is shown. (t-test ***p-value<0.001).

From: ML346: A Novel Modulator of Proteostasis for Protein Conformational Diseases

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