Methylene Blue, salubrinal or guanabenz
suppresses
paralysis during
ageing and extends
lifespan in ATXN3-CAG89 worms without affecting the expression level of this transgene. (A-C) The motor defect phenotype observed in ATXN3-CAG89 worms was significantly decreased in the presence of 60 μM MB (****P<0.0001), 50 µM Sal (****P<0.0001) or 50 µM Gua (****P<0.0001) [by log-rank (Mantel–Cox) test; n=270-300]. This experiment was replicated three times. (D) ATXN3-CAG89 worms showed an increase lifespan in the presence of 60 μM MB (****P<0.0001), 50 µM Sal (*P<0.05) or 50 µM Gua (****P<0.0001) [by log-rank (Mantel–Cox) test; n=300-360]. This experiment was replicated three times. (E) Total protein levels for transgenic worms expressing mutant ATXN3-CAG89 with and without exposure to Sal, Gua or MB. Antibody detection revealed signals for all four conditions. No differences in expression were observed between the untreated and treated transgenic worms. Actin staining was used as a loading control, and the expression ratio±s.e.m. of ATXN3 to actin was determined from three independent experiments. Representative western blots are shown. Gua, guanabenz; MB, Methylene Blue; Sal, salubrinal.