Fig. 4
From: Inhibition of SOD1 trimerization is a novel drug target for ALS disease
PRG-A-04 ameliorates ALS progression in the SOD1G93A−Tg mouse model. a The neuronal markers were maintained in mice receiving i.p. injection of PRG-A-04. Low expression of MAP2 was detected in vehicle (DMSO)-treated control mice. Representative images are shown at a magnification of 10 × , with inserts of 20 × (yellow box). Enlarged pictures of cervical and lumbar spinal cords are shown in Fig. S4g and S4i. The intensity of neuronal markers was counted and plotted in Fig. S4h and S4j. Scale bar, 20 μm. b Compared to DMSO-treated 17-week-old mice (Con, n = 4), PRG-A-04 reduced SOD1 aggregation with SOD1-positive vacuoles (red arrowheads) (20 mg/kg, n = 3, 50 mg/kg, n = 3). Scale bar, 20 μm. c Number of SOD1 inclusions was counted with SOD1-positive vacuoles. N.D., not detectable. **P < 0.01, ****P < 0.001. d The insoluble SOD1 was reduced by PRG-A-04 in the cervical spinal cord tissue lysates of mice carrying SOD1-G93A mutation. e The neuronal protective effect of PRG-A-04 was confirmed by microarray in spinal cord tissue. f Gene ontology analysis of spinal cord tissue between the vehicle- and PRG-A-04-treated SOD1G93A−Tg mice. g Kaplan Meier survival curve of SOD1G93A−Tg ALS mice. Compared to vehicle-treated mice (Con, n = 6), PRG-A-04 treatment by p.o. injection at 15 mg/kg (n = 4) and 25 mg/kg (n = 5) extended the survival by about 18 and 25 days, respectively. ***P < 0.005