PARP1 Inhibition with Olaparib for Metabolic Reprogramming in GSS Deficiency

PARP1 inhibition reduces NAD+ consumption, enhancing SIRT1-mediated activation of antioxidant gene programs. Simultaneously activates AMPK-mediated metabolic reprogramming toward pentose phosphate pathway, increasing NADPH production for alternative antioxidant systems (thioredoxin, peroxiredoxin) to compensate for glutathione deficiency.