Fig. 1. Aberrant JNK pathway activation in mouse models of ALS and in spinal cord tissue from patients with sporadic ALS. Aberrant JNK pathway activation.

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Fig. 1. Aberrant JNK pathway activation in mouse models of ALS and in spinal cord tissue from patients with sporadic ALS. Aberrant JNK pathway activation in mouse models of ALS and in spinal cord tissue from patients with sporadic ALS. (A) Representative images of p-c-Jun immunostaining in nonTg and SOD1G93A mouse spinal cords at 9 and 14 weeks of age. Black arrowheads highlight p-c-Jun–positive nuclei. Scale bar, 40 μm. (B) Mean number of p-c-Jun–positive cells per section in spinal cords from SOD1G93A mice at 9 and 14 weeks of age. *P < 0.05 and ***P < 0.001. (C) Representative double staining for p-c-Jun (green), NeuN (red), and DAPI (4′,6-diamidino-2-phenylindole)–positive nuclei (blue) in 14-week-old SOD1G93A mouse spinal cord tissue. White arrowhead points to a NeuN-positive motor neuron. Scale bar, 10 μm. (D) Dlk (green) expression colocalizes with Tubb3 (red) by in situ hybridization in nonTg mouse spinal cord. Scale bar, 50 μm. (E to G) p-JNK and p-c-Jun in lumbar spinal cord lysates from patients with sporadic ALS (sALS). (E) Western blot of p-JNK and p-c-Jun in spinal cord lysates from patients with sALS. (F) p-JNK (54- and 46-kDa isoforms) and p-c-Jun are elevated in spinal cord tissue from sALS patients versus healthy controls. **P = 0.0095, two-tailed Mann-Whitney test. (G) Ratios of phosphoprotein to total protein for JNK 54 kDa (JNK 54), JNK 46 kDa (JNK 46), and c-Jun are elevated in spinal cord tissue from sALS patients versus healthy controls. **P = 0.0095 and *P = 0.0190, Mann-Whitney test. (H and I) Staining for p-c-Jun in brain cortical tissue from TDP-43A315T transgenic mice, a model of ALS. (H) Representative images of p-c-Jun staining in the cortex of nonTg (left) and TDP-43A351T transgenic littermates (right). Scale bar, 100 μm. (I) Mean number of cortical p-c-Jun–positive cells in TDP-43A351T transgenic and nonTg littermates. *P < 0.05, two-tailed Student’s t test. Claire E. Le Pichon et al., Sci Transl Med 2017;9:eaag0394 Published by AAAS