Fig. 5. Putative pro-apoptotic mechanism in the spinal cord of the wobbler mouse at the clinical stage p40. P53 is known to bind to NDRG2 and induce its transcription. Therefore NDRG is associated with the apoptotic pathway of p53 [13]. MiR-375-3p inhibits the translation of p53 by directly targeting its mRNA [24]. Additionally, p53 expression is known to be increased in the spinal cord of the wobbler mice [15]. NDRG2 mRNA and protein expression was shown to be upregulated in the spinal cord of wobbler mice at p40. Since the expression of miR-375-3p is decreased, translation of p53 is not effectively inhibited, which affects NDRG2 transcription. High level of NDRG2 can lead to elevated ROS level, which in turn can activate p53. The increased p53 and NDRG2 level lead to increased apoptosis in the spinal cord of the wobbler mice.