Epilepsy CurrentsWatch Out for GATORs: Fasting, Seizures, and Nutrient Sensing

Decoding the Interplay of Fasting, mTOR, and Seizure Control

This article illuminates the critical function of fasting and mTOR regulation in the treatment of epilepsy by delving into the intricate molecular processes.

• Fasting may reduce hyperexcitability in epilepsy, paving the way for dietary therapies like the ketogenic diet.
• The regulatory protein mTOR plays a crucial role in neurochemical pathways associated with seizure control.
• In a non-fasting state, mTOR promotes protein and lipid synthesis, while fasting decreases mTOR activity, potentially reducing oxidative stress.
• mTOR inhibition is a significant target for reducing seizures, as evidenced by the approval of the mTOR antagonist everolimus for treating tuberous sclerosis complex (TSC).
• The mTOR complex 1 (mTORC1) is a crucial nutrient sensor; its overactivation can lead to seizures, which can be partially reduced by mTOR inhibition.
• DEP domain-containing protein 5 (DEPDC5), a component of the GATOR1 protein complex, may be a critical link between fasting and seizure reduction via mTORC1.
• Fasting increases neuroprotective proteins, decreases inflammatory cytokines, and enhances overall bioenergetics and neuronal resilience, suggesting potential signaling pathways contributing to the effect of fasting and the ketogenic diet on seizure control