FIGURE 2.

Apoptosis, autophagy, necroptosis, and pyroptosis in epilepsy. Panel (A) indicates apoptosis in epilepsy. Extensive investigations has illustrated elevations of oxidative stress, Forkhead box O3, p53, and c-Jun N-terminal kinase while decreased GABA_AR γ2 Serine 327 phosphorylation are reported to trigger neuronal apoptosis and subsequently promote epileptic phenotype. And many drugs including sodium valproate, pifithrin-a, N-acetyl-l-cysteine and supplement with ketogenic diet all counteract epileptic seizures via inhibiting apoptosis; panel (B) shows autophagy in epilepsy. Autophagy has dual effects on epilepsy. That is pro-epileptic and anti-epileptic roles. On the one hand, induction of autophagic response by high level of oxidative stress has been found to cause epilepsy. Diverse therapeutic interventions including ascorbic acid, vitamin E and ketogenic diet exert curative potential against epilepsy. On the other hand, autophagic activation by rapamycin has therapeutic effect against epilepsy via inhibition of mTOR; panel (C) shows necroptosis in epilepsy. Activations of RIP1, RIP3, MLKL, and phosphorylated MLKL have been reported to induce necroptosis and contribute to epileptogenesis. However, curcumin, aucubin or phenhydan^® suppresses epileptic seizures via inhibiting necroptosis; panel (D) shows pyroptosis in epilepsy. Activation of inflammasome and elevation of cannabinoid receptor type 2 have been observed to result in pyroptosis in animal models of epilepsy.