Using an unbiased metabolomics strategy and targeted gene expression analyses of wildtype and Npc1-/- brain tissue, we found i) significant alterations in glucose and pyruvate metabolism that suggested a pre-symptomatic decrease in the oxidative metabolism of glucose, and a compensatory increase in glycolysis with disease progression, and ii) a pre-symptomatic activation of astrocytic antioxidant response systems, which suggests that oxidative stress plays a key role early in NPC disease pathogenesis. This evidence concerns the gene NPC1 and nasopharyngeal carcinoma.