Mito-TEMPO improves survival rates in npc1-knockout zebrafish by reducing oxidative stress and enhancing mitophagy via Sod2

Most patients present with early-life symptoms including hepatosplenomegaly and digestive system impairment, followed by progressive neurodegeneration. However, effective therapeutic approaches to improve survival in NPC disease remain limited.

In this study, using a npc1-knockout (NPC1-KO) zebrafish model established in our laboratory, our team suggests that npc1-deficiency appears to correlate with marked downregulation of superoxide dismutase 2 (Sod2) expression, concurrent with excessive oxidative stress (OS), mitochondrial dysfunction, and defective mitophagy. Treatment with Mito-TEMPO, a mitochondria-targeted antioxidant acting on SOD, increased survival rates and ameliorated cholesterol accumulation and liver function impairment in early-stage NPC1-KO zebrafish.