Epilepsy and autophagy modulators: a therapeutic split

Area of Science:

• Neuroscience
• Cellular Biology
• Pharmacology

Background:

• Epilepsy is a neurological disorder marked by recurrent seizures, with one-third of patients experiencing refractory epilepsy unresponsive to anti-epileptic drugs (AEDs).
• Macroautophagy/autophagy, a cellular degradation process, is implicated in epilepsy pathogenesis, potentially by regulating neurotransmitter balance.

Purpose of the Study:

• To review the role of autophagy in the development and progression of epilepsy (epileptogenesis) and in established epilepsy.
• To discuss how autophagy modulators (inducers and inhibitors) impact epileptogenesis and epilepsy.

Main Methods:

• Mini-review of existing literature on autophagy's role in epilepsy.
• Analysis of studies investigating autophagy inducers and inhibitors in the context of epilepsy and status epilepticus (SE).

Main Results:

• Autophagy appears to protect against epileptogenesis, but its role in status epilepticus (SE) is complex, suggesting a dual effect.
• Autophagy inducers may reduce seizure frequency and severity, positioning them as potential adjuvant therapies for epilepsy.
• Conversely, autophagy inhibitors have demonstrated anticonvulsant effects, highlighting the intricate involvement of autophagy.

Conclusions:

• Autophagy modulation presents a promising therapeutic avenue for epilepsy management, particularly for refractory cases.
• Further research is needed to elucidate the precise mechanisms and optimize the use of autophagy modulators for treating epilepsy and SE.