Fig. 6: Pharmacological inhibition of DLK reduces c-Jun phosphorylation and blocks neuronal apoptosis in demyelinated MyrfΔiSox10 mice.
From: Remyelination protects neurons from DLK-mediated neurodegeneration
a Schematic of the DLK MAPK cascade and timeline of GNE-3511 administration. b Serum levels of GNE-3511 following 3 days of oral gavage. c Representative retinal flatmount images of vehicle and GNE-3511 treated mice stained with phosphorylated c-Jun and RBPMS at 10 weeks post-tamoxifen. d Overview of retinas with locations of cleaved caspase-3+ cells in the ganglion cell layer (GCL) indicated by black X. e Quantification of phosphorylated c-Jun+ cells in vehicle or GNE-3511-treated retinae. ****p < 0.0001. Vehicle Myrffl/fl n = 8, MyrfΔiSox10 n = 11 and GNE-3511 Myrffl/fl n = 6, MyrfΔiSox10 n = 9. f Cleaved caspase-3 density in vehicle or GNE-3511-treated retinae. ***p = 0.0002 and ****p < 0.0001. g Cleaved caspase-3+RBPMS+ cell density in vehicle or GNE-3511-treated retinae. Vehicle-treated MyrfΔiSox10 relative to GNE-treated MyrfΔiSox1 mice at 10 weeks post-tamoxifen (p = 0.0005) and relative to Myrffl/fl controls (vehicle, p = 0.0008, GNE-3511, p = 0.0001). Vehicle Myrffl/fl n = 7, MyrfΔiSox10 n = 7 and GNE-3511 Myrffl/fl n = 6, MyrfΔiSox10 n = 6 mice in (f, g). Two-way ANOVA with Tukey’s post hoc for individual pairwise comparisons in (e–g). All statistical tests are two-sided. Error bars are SEM. Scale bars are 50 µm in (c) and 500 µm in (d). Source data for this Figure are provided as a Source Data file. a created in BioRender. Duncan (2023) BioRender.com/h30g439.
