Epilepsy and autophagy modulators: a therapeutic split.

Epilepsy is a neurological disease characterized by repeated unprovoked seizure. Epilepsy is controlled by anti-epileptic drugs (AEDs); however, one third of epileptic patients have symptoms that are not controlled by AEDs in a condition called refractory epilepsy. Dysregulation of macroautophagy/autophagy is involved in the pathogenesis of epilepsy. Autophagy prevents the development and progression of epilepsy through regulating the balance between inhibitory and excitatory neurotransmitters. Induction of autophagy and autophagy-related proteins could be a novel therapeutic strategy in the management of epilepsy. Despite the protective role of autophagy against epileptogenesis and epilepsy, its role in status epilepticus is perplexing and might reflect its nature as a double-edged sword. Autophagy inducers play a critical role in reducing seizure frequency and severity, and could be an adjuvant treatment in the management of epilepsy. However, autophagy inhibitors also have an anticonvulsant effect. Therefore, the aim of the present mini-review is to discuss the potential role of autophagy in the pathogenesis of epileptogenesis and epilepsy, and how autophagy modulators affect epileptogenesis and epilepsy. AD: Alzheimer disease; AEDs: antiepileptic drugs; AMPK: adenosine monophosphate-activated protein kinase; ER: endoplasmic reticulum; GABA: gamma aminobutyric acid; HCQ: hydroxycholoroquine; IP: inositol 1,4,5-trisphosphate; NSAID: non-steroidal anti-inflammatory drug; PI3K: phosphoinositide 3-kinase; ROS: reactive oxygen species; SE: status epilepticus; PTZ: pentylenetetrazole; TLE: temporal lobe epilepsy; TSC: tuberous sclerosis complex.