In contrast, the levels of p-AKT and p-FoxO3a were significantly elevated in the combination treatment group (P < 0.0001 for both) (Figures 12A–D), suggesting that VPA and ALA synergistically activate the PI3K/AKT/FoxO3a pathway, which may contribute to their observed neuroprotective effects in ALS. Here, FOXO3 is linked to amyotrophic lateral sclerosis.