Fig. 5
From: Autophagy and autophagy signaling in Epilepsy: possible role of autophagy activator
Mechanistic effects of autophagy inducers in epilepsy: Rapamycin inhibits mTORC1 and attenuates T cell migration and development of neuroinflammation which trigger epilepsy. Additionally, Rapamycin activates the FK506-binding protein that regulates gamma-aminobutyric acid (GABA) ergic neurons and expression of glutamate receptors in astrocytes thereby reducing seizures. Metformin has anti-seizure activity by activating 5’ AMP-activated protein kinase (AMPK) signaling and inhibiting mTOR pathways which are dysregulated in epilepsy. AMPK improves the expression of glucose transporter 1 (GLUT1) and peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1α) which improves mitochondrial biogenesis, and upregulates Sirtuin1 (SIRT1), Forkhead box O3 (FOXO3), progranulin and GABA which induce neuroprotection. Ibuprofen has a neuroprotective and anti-seizure effect by inhibiting cyclooxygenase (COX) and heat shock protein 90 (Hsp90) for the induction of autophagy. Lithium inhibits the expression and activity of glycogen synthase kinase-3 beta (GSK3β) and inositol trisphosphate (IP3) which are the negative regulators of autophagy