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REVIEW

mTOR inhibition in epilepsy: A literature review

Lip-Yuen Teng1* ,  Min Jung Chang2,3,4 ,  Se Hee Kim5*
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1 Pediatric Neurology, Department of Pediatrics, Hospital Tuanku Ja’afar, Seremban, Malaysia
2 Department of Pharmacy and Yonsei Institute of Pharmaceutical Science, College of Pharmacy, Yonsei University, Incheon, Republic of Korea
3 Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of Medicine and Pharmacy, Yonsei University, Incheon, Republic of Korea
4 Graduate Program of Industrial Pharmaceutical Science, Yonsei University, Incheon, Republic of Korea
5 Pediatric Neurology, Department of Pediatrics, Yonsei University College of Medicine, Epilepsy Research Institute, Severance Children’s Hospital, Seoul, Republic of Korea
Advanced Neurology 2024, 3(3), 3568 https://doi.org/10.36922/an.3568
Submitted: 3 May 2024 | Accepted: 19 June 2024 | Published: 29 August 2024
(This article belongs to the Special Issue Advances in the pathogenesis, diagnosis and treatment of epilepsy)
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Hyperactivation of the mammalian target of the rapamycin (mTOR) pathway causes epilepsies, neurodevelopmental disorders, and malformations of cortical development, collectively known as mTORopathies. These conditions arise from loss-of-function variants in negative regulators or gain-of-function variants in positive regulators of the mTOR pathway. Conventional antiseizure medications mainly target downstream effectors such as ion channels or neurotransmitter activity to suppress seizures. On the contrary, extensive pre-clinical and clinical evidence has demonstrated that mTOR inhibitors have anti-epileptogenic or disease-modifying effects, potentially preventing epilepsy or slowing disease progression rather than merely controlling seizures. In general, mTOR inhibitors bind to mTOR protein, preventing its interactions with substrates and disrupting mTOR complex assembly, thereby suppressing downstream activities. In this review, we provide a comprehensive overview of the mTOR signaling pathway, outline the spectrum of mTORopathies and its subset (GATORopathies), and highlight the clinical applications of mTOR inhibitors, particularly everolimus, along with other potential mTOR-modulating agents.

Keywords
mTOR
Epilepsy
Tuberous sclerosis
Rapamycin
Everolimus
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
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Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing
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